Frequency Therapeutics — Hearing Loss Regeneration

So what you're stating in simple terms is that as long as you have hair cells then there is an ability for these to regrow with FX-322 treatment?

 

As long as you have LGR5+ support cells, you can regrow hair cells. And mostly you won't lose all of those until you have profound loss (greater than 90dB).

 

I've read somewhere about 3D printed "needles" that could be small and flexible enough to deliver the payload needed further. Seeing Otomagnetics and other similar companies approaches, think they will be approved later since they are viewed as a treatment in itself that goes through the normal 3 phases for approval.

 

@FGG What are your thoughts that so far they have sort of proved that FX-322 is working for word recognition tests implying they are able to grow inner hair cells. However, the latest study showed no benefit in standard audiogram testing implying it didn't do anything for outer hair cells?

Also, the study by Audion Therapeutics showed an improvement in 40% of patients, again was this speech recognition tests or actual testing across the frequencies?

Do you think the September 30th completion date will be postponed with the whole COVID-19 situation?

Also, do you think if the completion date is September 30th, does that mean the public will have access to the results on that date?

Thanks.

 

I guess I'm thinking more in the way of altering the cell in such a way that the immune system (which can still see the cell) no longer thinks it's an invader. This is probably a pipe dream. Another minute possibility is that the immune system doesn't hate the support cell, which is what's taking the place of the damaged hair cell.

 

They have proven with pre-clinical and explant studies, the drug grows outer hair cells. I'm sure if they had measured 8000 Hz to 16000 Hz in phase 1, you'd see a lot of audiogram changes.

Who knows what Audion's precise results were, they haven't reported them.

Frequency noted a COVID-19 related delay in their last Fireside (archived on their website if you want to listen) so it will be later than September 30th. They hope to keep that delay as minimum as possible though.

 

My guess is it would be phenotypically similar enough that the immune system would still react. Ideally, getting the immune reaction subdued first would really help. Did you get a diagnosis?

 

I thought they did see 8kHz improvement in some?

 

They did (at 8kHz). @FGG is just referring to the UHF range which is commonly referred to as "8-16kHz" because that's the range that the extended audiogram tests for.

 

Only in 4 of the 15 (see slide 23): https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1
The hope is more improvements will be seen in other patients when they measure the higher ranges. Also, these improvements were seen at the 90 day mark. In the Phase 2a study they're measuring out to day 210. I'm curious if the people in the Phase 1/2 study saw improvements after the 90 day mark.

 

Strange that they only tested up to 8kHz when they know their drug is working foremost in the high frequencies.

 

I thought the same originally. However, the purpose of Phase 1 was really just to evaluate the safety profile (as is the case with most drugs like this). Even David Lucchino, CEO, said that gauging safety was really the only goal of the initial phase.

Phase 2a results will show us how effective FX-322 really is. We know it works, but how much does it work? That’s the question we will soon have the billion-dollar answer to.

 

True, but they were testing efficacy on the speech spectrum. I suspect they thought they would get further down into the ear than they did.

 

Not that strange I think. A test up to 8kHz is a standard hearing test. Audiologists hardly test beyond that. The evidence that hearing >8kHz is profoundly beneficial for day to day life is much less compelling than <8kHz.

 

Though the odd thing is that they went public right after those results were released, so you think they would be incentivized to show the drug works. Now that I think about this a little more, the cynical part of me thinks they only tested the lower range because if it showed improvement, it would imply improvement in the higher range too and the stock would have gone gangbusters. However, if they would have tested the higher range and the results weren't very good, it would reflect poorly on the drug in a study where they were mainly looking at safety.

 

It’s a shame because a lot of tinnitus resides in upper frequencies. According to a standard audiogram, I have perfect hearing. The model is so outdated. All frequencies matter.

 

Yeah I get it. The difficulty is that after a certain age most people have some hearing loss >8kHz. Most of them don’t have tinnitus though.

 

Right. I think how quickly you lose hearing can play a role in causing tinnitus. For a lot of people here, an acoustic trauma causing abrupt hearing loss results in tinnitus. It’s like a shock to the system. While this is not always the case, it seems that this occurs much more often than people waking up one day with tinnitus as a result of age.

 

If UHF audiograms were common I could see that, but most ENTs don't test for that. Now they have ammo to include it (and thus use centers that have that capability) in the extended arm.

 

Some points probably worth noting about that though.

1. The 4/15 is in consideration of the total that took FX-322 rather than the placebo. Again above this there is half of these who were given the high dose and half who were given the low dose. Data indicates that those given the higher dose did likely benefit from the improvement moreso than the ones consuming the low dose volume. Hence why Frequency is proceeding with the higher dose in the trial that is active. As such this is more like 4/7 or so which would be classed positively. Again note that there was only one ear done due to the trial parameters and actually this tends to show that we would likely see even further benefit being delivered if both ears got treated.

2. There tends to be a theory that the higher dose does seem to be more effective in providing beneficial outcomes. Obviously this is why they are trying other improved dosing mechanisms like repeat dosing, multiple dosing and reformulating dosing to improve not only the amount given but the way which the dose is delivered. I think that this is a key in the treatment effectiveness cause it is already proven that more volume of drug leads to more improvement and such provides better results. As such I feel we are likely to tend to see further improvements over time.

This could be for a number of reasons such as the gel is able to disseminate further, more drugs results in greater growth and also that the drug targets the area needing treatment first and thus won't treat the cochlear further until it has regrown the cells at front.

3. The word recognition improvement in those tested tended to be excellent essentially showing that the treatment was successful and also helping as per the intended purpose of the substance.

4. The testing to day 210 is for multiple reasons really. These include checking the treatment that has taken place has provided improvement and also a subject is maintaining their level as in the inaugural trial. There is evaluation at multiple points also actually to confirm the benefits of multiple doses, whether they are also seeing improvement at the different points after treatment, to approve the determination to date that regrowth takes place till 90 days since the dose, that the treatment benefit is still maintained and that there is positive health outcomes for patients put through multiple shots in their ear.

5. The treatment to date has shown it works and thus the trial will be focused on improving that in participants to get the best results. Rather than being a case of only needing to see whether this treatment works it is now a case of this treatment works but how to make it work the best.

Thus considering they have only conducted minimal trials to this point as well as conducting the relevant scientific evaluations to show that the treatment is doing what they want it to do through medical and lab inspections, it is fairly likely that this will provide benefit and positive outcomes.

 

Technically speaking, if this works, wouldn't it be a good idea for all moderate and severe tinnitus sufferers to get this just to make certain that we have as good of hearing as we can to prevent tinnitus from getting worse?

 

I was thinking for those four patients who showed clinical meaningful improvements, they could have asked them back and did a UHF audiogram? It is quite easy...

 

Well I don't see why they wouldn't be able too. Regardless, just because you age does not mean you will develop high frequency tinnitus.

 

Being scientists, knowing what area the drug would have to pass through first, it doesn't instill much confidence in their scientific endeavours that no one thought of doing this... It's a 5 minute job.

 

You'd need a time machine to get the 'before' measurements to compare though.

 

It's not the time involved.

At least in the US where this study is taking place, it's highly unusual for clinics to have this ability. I live in a reasonably large area and I had to go across many states to get a high frequency audiogram done. Not because of the time involved but because the equipment wasn't calibrated for the UHF testing.

Edit: for anyone looking to get UHF testing done themselves, if I had known to go into a university setting, I could have gotten this done earlier. My mistake was trying to get UHF through regular ENT clinics.

 

Blasphemy, you dare question the Demi gods of hearing regeneration?

 

Thanks for asking this. I had the same question but did not know how to ask.

I got severe tinnitus by the time I found out what ototoxicity even was - and then I still had to find a way off all the drugs I was on.

Horrible dilemma.

Best wishes.

 

It isn't clinically relevant as it isn't actually part of a standard hearing measure. Also again actually with the results reported it is fairly evident that they had improvement in those frequencies.

 

So maybe it’s because they only did the pre FX-322 audiograms up to 8kHz.