Frequency Therapeutics — Hearing Loss Regeneration

I'm not the one calling for FX-322 to be "burned to the ground". It will play out however it plays out. Heck, even if Neuromod magically versions up Lenire to the point where it actually works unequivocally and eliminates risk of "disimprovement" I'll reconsider them as well.
Why so defensive?
 
I'm quite shocked that the age-related hearing loss trial wasn't successful.

If the severe hearing loss trial isn't successful as well, that means they will try and run the trial only for mild-moderately severe patients as previous trials with these patients were successful. I'm glad they are sticking with the single dose moving forward and finding out which patients will benefit from FX-322.

I'm hoping PIPE-505 results coming out this month are positive. Having PIPE-505 regrow synapses and some OHCs in addition to FX-322 regrowing IHCs and some OHCs should solve most of our problems such as hyperacusis, tinnitus and hearing loss.

If PIPE-505 goes into Phase 2 as soon as their Phase 1 results come out, we could be seeing a similar timeline with FX-322 where both drugs come out in the market at the same time.

I do wonder if the key to solving our issues is that we need both FX-322 and PIPE-505 injected.
 
Why so defensive?
You obviously haven't been paying attention to the thread--namely the part where someone tried to essentially banish me from it. That might make one defensive, don't you think? Anyway, I have to imagine most reading this thread do not want to read all of this member on member drama. It's all noise.
 
I'm quite shocked that the age-related hearing loss trial wasn't successful.

If the severe hearing loss trial isn't successful as well, that means they will try and run the trial only for mild-moderately severe patients as previous trials with these patients were successful. I'm glad they are sticking with the single dose moving forward and finding out which patients will benefit from FX-322.

I'm hoping PIPE-505 results coming out this month are positive. Having PIPE-505 regrow synapses and some OHCs in addition to FX-322 regrowing IHCs and some OHCs should solve most of our problems such as hyperacusis, tinnitus and hearing loss.

If PIPE-505 goes into Phase 2 as soon as their Phase 1 results come out, we could be seeing a similar timeline with FX-322 where both drugs come out in the market at the same time.

I do wonder if the key to solving our issues is that we need both FX-322 and PIPE-505 injected.
Does PIPE-505 regenerate (create new hair cells) hair cells? Or does it cure damaged hair cells?

FX-322 creates new hair cells.

If so, can these two drugs be divided into roles?
 
Does PIPE-505 regenerate (create new hair cells) hair cells? Or does it cure damaged hair cells?

FX-322 creates new hair cells.

If so, can these two drugs be divided into roles?
It's not very clear, but PIPE-505 is believed to cause some support cells to differentiate into OHC. Thereby depleting the support cells. Somehow it also causes existing OHC to regenerate missing synapses.

If successful, I could see it being used after FX-322 treatment. FX-322 would cause mitosis of the progenitor cells; creating new hair cells that synapse. PIPE-505 would then cause any existing hair cells that were functioning with missing synapses to synapse.
 
It's not very clear, but PIPE-505 is believed to cause some support cells to differentiate into OHC. Thereby depleting the support cells. Somehow it also causes existing OHC to regenerate missing synapses.
It seems to be the same "Forced Differentiation" as Audion Therapeutics. It looks like γ-secretase inhibitor. In terms of depletion of support cells, I think OTO-413 is better in combination with FX-322.
 
It's not very clear, but PIPE-505 is believed to cause some support cells to differentiate into OHC. Thereby depleting the support cells. Somehow it also causes existing OHC to regenerate missing synapses.

If successful, I could see it being used after FX-322 treatment. FX-322 would cause mitosis of the progenitor cells; creating new hair cells that synapse. PIPE-505 would then cause any existing hair cells that were functioning with missing synapses to synapse.
Just to clarify, PIPE-505 would regenerate the Type 1 synapses which connect to the inner hair cells. The OHCs synapse onto Type 2s, which are not involved in synaptopathy.
 
I haven't been a part of this thread and don't want to join the criticism circus but like every other person on this site, I want a cure or at least a viable treatment. It's likely that some members are overly optimistic and holding on to hope as a coping mechanism and others are too pessimistic, not giving the research a chance to produce results. It's important that there remains a balance; we shouldn't get ahead of ourselves but we shouldn't sabotage the process either. If people want to believe in this and hold on as a coping mechanism, that's their choice. In the event that things go south they will likely be worse off than before but in the meantime they have something to believe in and a reason to move forward with their lives. It's not for others to say how someone should feel and whether they should believe in this treatment or not, just like you shouldn't judge someone on their political views or religious affiliation. Everyone has a different opinion and no single opinion is correct, because it's an opinion and not scientific fact.

What is important is that everyone should realize that just because results are not favorable, it doesn't mean that the research was done in vain. Whether a trial/product is successful or a failure, we still get data from the trial. We can reformulate, we can look at different delivery methods, we can partner with a third party, we can adjust dosing, etc. It's important for these trials to push ahead whether or not people believe they will have positive, legitimate results. The community needs the research and at the end of the day, no one should be offended as to how things proceed. Frequency Therapeutics is not "selling" anyone a product, except for their stock, and you are not obliged to buy in to it. If in the future they release a product, you will have the opportunity to decide whether the rewards outweigh the risks and if the investment is worth it for the efficacy of the drug.

Even products like Lenire shouldn't be entirely discounted. Yes, it's a letdown that the product didn't work as promised but ultimately there is another product on the market and there is research surrounding it providing data to researchers. We need to stop seeing everything as a failure and be thankful that people and companies are trying to put drugs and products out to market, even if they don't have high efficacy thresholds. Everyone told Steve Jobs he was crazy when coming out with the iPhone, they said it wasn't perfect and didn't fit Apple's reputation. Some almost 20 iterations later and today we have a device that is pretty much as perfect as technology will allow for (it's a metaphor Samsung fanboys, just chill). Medical progress is no different, it needs to start from somewhere, even if that starting point is a failure.

Let's just give this thigh a chance and stop arguing about who is right and wrong and whether FX-322 will prevail or fail.
 
Could you show me where you found this?

Thanks.

https://www.pipelinetherapeutics.com/news/Society-for-Neuroscience-49th-Annual-Meeting-Chicago.pdf

It says right here that PIPE-505 leads to regeneration of inner hair cell ribbon synapses aka Type 1s. When people refer to synaptopathy, it refers to the these connections. These are the connections that have been implicated in hidden hearing loss and tinnitus/loudness hyperacusis, if lost. It has been established that the Type 2 ribbon synapses can in fact increase in number following acoustic trauma, whilst the Type 1s decrease - so essentially they have opposite reactions to acoustic trauma.

Acoustic Trauma Increases Ribbon Number and Size in Outer Hair Cells of the Mouse Cochlea
 
https://www.pipelinetherapeutics.com/news/Society-for-Neuroscience-49th-Annual-Meeting-Chicago.pdf

It says right here that PIPE-505 leads to regeneration of inner hair cell ribbon synapses aka Type 1s. When people refer to synaptopathy, it refers to the these connections. These are the connections that have been implicated in hidden hearing loss and tinnitus/loudness hyperacusis, if lost. It has been established that the Type 2 ribbon synapses can in fact increase in number following acoustic trauma, whilst the Type 1s decrease - so essentially they have opposite reactions to acoustic trauma.

Acoustic Trauma Increases Ribbon Number and Size in Outer Hair Cells of the Mouse Cochlea
I wonder if regrowing IHC Type 1 ribbon synapses will reduce OHC Type 2 ribbon synapses once you get PIPE-505 injected.
 
I wonder if regrowing IHC Type 1 ribbon synapses will reduce OHC Type 2 ribbon synapses once you get PIPE-505 injected.
I have wondered this too although it's important to point out that there are a lot of unanswered questions - see this talk Megan Wood gave from 32:00 onwards where she addresses these. E.g it is not known whether this effect persists or not and how things like inflammation or cell death could affect OHC ribbons.

 
I have wondered this too although it's important to point out that there are a lot of unanswered questions - see this talk Megan Wood gave from 32:00 onwards where she addresses these. E.g it is not known whether this effect persists or not and how things like inflammation or cell death could affect OHC ribbons.
Hopefully we will have some answers soon in the upcoming years.
 
I have wondered this too although it's important to point out that there are a lot of unanswered questions - see this talk Megan Wood gave from 32:00 onwards where she addresses these. E.g it is not known whether this effect persists or not and how things like inflammation or cell death could affect OHC ribbons.
Interesting stuff. It will be a while before it is known if cell regeneration / synaptogenesis in other areas of the cochlea leads to a reversed change in those cells / synapses that changed from noise damage. I would think in the case of OHC suspected to cause hyperacusis / pain, that more new OHC properly synapsed to the Type 2 nerve alongside damaged/"oversynapsed" may help at least dampen the effect of hyperacusis. Just a theory.

There hasn't been any evidence so far from OTO-413 or FX-322 of patients with NIHL (which most of them had), either experiencing hyperacusis as a new event, or it worsening. I would think that hyperacusis would fall into a significant adverse event, where most reported are temporary/transient and related to the injections.
 
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I found this slide particularly interesting. If I am understanding it correctly, the red dots represent OHC all connected to the same Type 2 nerve fiber running along the cochlea starting at the base.

I did not expect this based on prior diagrams. I had a prior understanding that the OHC were connected horizontally across their neighbors, not in this long avenue along the cochlea. Then, connected just past the adjacent IHC (not pictured). Which is a pretty short distance.

Thinking about FX-322 not showing audiogram changes, even though they had observed OHC regrown in-vitro, (which are noted to be observed on the audiogram), I wonder now if at the highest frequencies near the apex, the Type 2 fiber just isn't that high anymore to connect to the newly generated OHC.

In this example, we see that farthest out red dot, indicating the highest frequency OHC observed on the Type 2 nerve tested. However, if say an OHC is regenerated in the white region nearest to the apex, and if any belonged to the Type 2 fiber shared with the other red OHC, would they be able to reach the nerve and resynapse as expected?

Perhaps that's why they saw those few responders show improvements at 8 kHz on the audiogram. Because the OHC regenerated in those spaces could easily re-synapse with the Type 2 nerve already in-between a few other existing OHC located "above" and "below" that regenerated cell.
 
Are we expecting any new data to be presented. Boy they have a lot of studies that should have data rolling in shortly.

Also does anyone know off-hand (and I know that you do), are the 111,112, and 113 studies with a single injection?
The trials are scheduled to be completed this month. I expect good results. Otherwise if no results, they will only be putting out a press release...

Yes, all the studies are with a single dose.

Forget about 112, (age-related hearing loss) it already failed.

Our focus is on 111 and 113 (currently ongoing) which will define the Phase 2 study.
 
Interesting that they are now saying, "Upcoming Phase 2 Trials" (plural) for FX-322.
 
Where are they saying that?
1. On the Jefferies webcast just now
2. In the June Investor Presentation: Page 18

"Anticipate activating additional FX-322 Phase 2 placebo-controlled studies in H2 2021"

https://investors.frequencytx.com/static-files/5805963a-0f32-449f-8c29-ba6b7356cd0a

Based on the Q&A, it sounds like Lucchino is pretty confident that Moderate -> Severe SNHL is going to be the target patient population for one of the "New Phase 2" studies.

I wonder what another one might be?
 
I can't believe no one asked questions! My question was the only one!

I asked:

When can we expect the severe study results? And how confident are you that the moderate and severe hearing loss patients will respond to the drug?

(You have to watch the presentation to see his answer) :)
 

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