Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

Here's what confuses me. Four out of four available responders return at months 8-12 and see enough regression to be within their baseline margin of error. So in one breath, they are saying gains are maxed at a few months before they become trivial.

Then they are also saying that four different patients saw their major improvements later on that were observed at months 8-12. Are we to then predict that at months ~16-24 (so 8-12 months after their "response" recording at 8-12 months), these people should also regress to their original baseline margin of error?

What are we seeing here? It doesn't make any sense to me. So an equal number of people improve as regress in an open-label study. Seems pretty unclear if this means anything.

IMO - The severity of the hearing loss may be a factor.

 

[Tau]

Great news, and then this in the middle of the press release:

"Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance."

What the hell is going on with this drug?

Maybe synapses are not restored in large enough numbers even after the growth of new IHCs? I see no PTA results, I would expect the audiograms to be at least slightly better.

 

[ploughna]

Great news, and then this in the middle of the press release:

"Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance."

What the hell is going on with this drug?

Just thinking out loud here, but if they were only barely above the statistically significant threshold to begin with, it wouldn't take much of a reduction in improvement to put them below it. IIRC, the long term measurements of the phase1 participants all showed small reductions over time, but those results were a lot stronger leaving those patients still safely in positive territory. Bottom line seems to be more testing needed!

 

[Philip83]

Here's what confuses me. Four out of four available responders return at months 8-12 and see enough regression to be within their baseline margin of error. So in one breath, they are saying gains are maxed at a few months before they become trivial.

Then they are also saying that four different patients saw their major improvements later on that were observed at months 8-12. Are we to then predict that at months ~16-24 (so 8-12 months after their "response" recording at 8-12 months), these people should also regress to their original baseline margin of error?

What are we seeing here? It doesn't make any sense to me. So an equal number of people improve as regress in an open-label study. Seems pretty unclear if this means anything.

Yeah, this is very confusing, and not very assuring, to me as well...

 

[ColinUK]

Just let's all get injected and see what happens

 

[Ed209]

Here's what confuses me. Four out of four available responders return at months 8-12 and see enough regression to be within their baseline margin of error. So in one breath, they are saying gains are maxed at a few months before they become trivial.

Then they are also saying that four different patients saw their major improvements later on that were observed at months 8-12. Are we to then predict that at months ~16-24 (so 8-12 months after their "response" recording at 8-12 months), these people should also regress to their original baseline margin of error?

What are we seeing here? It doesn't make any sense to me. So an equal number of people improve as regress in an open-label study. Seems pretty unclear if this means anything.

I think we have to wait and see what comes out. I'm not their greatest fan when it comes to communication, but I'm interested to learn more.

 

[Cernuto]

Clearly Frequency Therapeutic botched the clinical.

Just let's all get injected and see what happens

Yes, and I don't even care about the hearing loss aspect of it.

 

[tommyd87]

Clearly Frequency Therapeutic botched the clinical.

Why do you think Frequency Therapeutics botched the clinical?

 

[Chad Lawton]

Great news, and then this in the middle of the press release:

"Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance."

What the hell is going on with this drug?

This is somewhat inline with their Phase 1/2 results where most of the patients saw a small regression after a year or two but 3 of the 5 patients still managed to stay in the statistically significant category. Maybe some of the initial benefit fades after awhile but you are still better off than before you go the drug.

 

[patorjk]

Here's what confuses me. Four out of four available responders return at months 8-12 and see enough regression to be within their baseline margin of error. So in one breath, they are saying gains are maxed at a few months before they become trivial.

Then they are also saying that four different patients saw their major improvements later on that were observed at months 8-12. Are we to then predict that at months ~16-24 (so 8-12 months after their "response" recording at 8-12 months), these people should also regress to their original baseline margin of error?

What are we seeing here? It doesn't make any sense to me. So an equal number of people improve as regress in an open-label study. Seems pretty unclear if this means anything.

It looks to me like they're spinning the news and burying the lede. I saw the headline and thought it was good news, I was confused as to why the stock dropped. Then I read the full release and saw that sentence. It's very disconcerting. It almost seems like the threshold they're using for statistical significance is too low and it's capturing noise. I suppose they do have the untreated ear to act as a placebo, but are they injecting anything into that ear (i.e, do the patients know which ear gets the drug)?

 

[Jurger]

Here's what confuses me. Four out of four available responders return at months 8-12 and see enough regression to be within their baseline margin of error. So in one breath, they are saying gains are maxed at a few months before they become trivial.

Then they are also saying that four different patients saw their major improvements later on that were observed at months 8-12. Are we to then predict that at months ~16-24 (so 8-12 months after their "response" recording at 8-12 months), these people should also regress to their original baseline margin of error?

What are we seeing here? It doesn't make any sense to me. So an equal number of people improve as regress in an open-label study. Seems pretty unclear if this means anything.

They definitely put a spin on the headline. Getting kinda tired of this drug. No PTA improvements and no durable word scores. It's ridiculous when compared to the hype when this all started.

 

[Cernuto]

Why do you think Frequency Therapeutics botched the clinical?

Two reasons. Poor job of weeding out candidates and a poor dosage schedule.

 

[tommyd87]

Two reasons. Poor job of weeding out candidates and a poor dosage schedule.

The candidacy issue is indeed Frequency Therapeutics' issue.

The dosage schedule not so much. Majorly difficult to know and/or predict how a medicine will operate until it is trialled.

 

[kiki]

They definitely put a spin on the headline. Getting kinda tired of this drug. No PTA improvements and no durable word scores. It's ridiculous when compared to the hype when this all started.

Did they measure PTA in FX-322-111?

Or are they not announcing it because there are no significant improvements?

 

[d'Wooluf]

They definitely put a spin on the headline. Getting kinda tired of this drug. No PTA improvements and no durable word scores. It's ridiculous when compared to the hype when this all started.

Pure bullshit spin. Nine people achieved statistically significant improvements at some point in the trial! Pity that at least four of them fell below statistical significance later on. Put it in two separate paragraphs and hope nobody notices.

 

[aorelia]

Interesting results. I wonder if any of these participants that had improvements in hearing had tinnitus as well.

 

[Cernuto]

The candidacy issue is indeed Frequency Therapeutics' issue.

The dosage schedule not so much. Majorly difficult to know and/or predict how a medicine will operate until it is trialled.

How about don't do another dose until the current dose shows efficacy and stabilization? What's majorly difficult to know about that?

 

[Ed209]

Pure bullshit spin. Nine people achieved statistically significant improvements at some point in the trial! Pity that at least four of them fell below statistical significance later on. Put it in two separate paragraphs and hope nobody notices.

This is what I've never liked about the company; they are never clear and consistent with their information. If you say that here, though, you can expect to get a hard time about it. Some of their previous news outputs have been so unclear that it has led to pages of debate and speculation on here. I want to see detail beyond their latest news statement before I pass judgement.

As for the stock, I didn't like how the directors were dumping theirs. It's not a good look for an early-stage biotech company. If they were confident about what they had, they'd be holding onto that shit.

 

[tommyd87]

How about don't do another dose until the current dose shows efficacy and stabilization? What's majorly difficult to know about that?

I don't think that there was any evidence at the time to demonstrate that the multi dosing would result in adverse outcomes which was why Frequency Therapeutics ran with it.

It is also the case that Frequency Therapeutics did do only single dosing as an element of their mucked up Phase 2 trial too. The troubles with the outcomes appear on face value to stem from the way they determined the participants much more so that with the dosing.

This is somewhat inline with their Phase 1/2 results where most of the patients saw a small regression after a year or two but 3 of the 5 patients still managed to stay in the statistically significant category. Maybe some of the initial benefit fades after awhile but you are still better off than before you go the drug.

Which is also consistent with their claims/theory that there would be a need to obtain booster/follow up dosings.

 

[grate_biff]

Two reasons. Poor job of weeding out candidates and a poor dosage schedule.

Poor delivery, maybe too weak concentration of compound!

 

[Keith Handy]

If you say that here, though, you can expect to get a hard time about it.

You need to stop making every post about other people here who have disagreed with you. This obsession is unhealthy.

 

[Ed209]

You need to stop making every post about other people here who have disagreed with you. This obsession is unhealthy.

That's a bit of a one-sided exaggeration. I haven't posted that much in this thread, so I wasn't really referring to my posts, but all the other reactions I've seen. From what I've read, whenever anyone has criticised Frequency Therapeutics, it's been met with a pretty hardline defence of the company, even though they bring these criticisms on themselves, in my opinion.

In what way are all my posts about people disagreeing with me? I've engaged in some debate, for sure, but isn't that what forums are all about? I've given Frequency Therapeutics a bit of stick, but that's just my opinion of them based on the news statements they release and their stock activities. It's nothing personal (unless there are people here who actually work for them or something ).

 

[Jurger]

Apparently they are contacting patients who didn't get into previous trials that their next trial is about to start (source: people on Facebook).

 

[Keith Handy]

From what I've read, whenever anyone has criticised Frequency Therapeutics, it's been met with a pretty hardline defence of the company, even though they bring these criticisms on themselves, in my opinion.

Once again, it's about the other people on the forum, even in response to me trying to point out that you're obsessed with the other people on the forum. I don't think you can write a post about the drug or the company without alluding to your disappointment in other people here.

 

[patorjk]

That's a bit of a one-sided exaggeration. I haven't posted that much in this thread, so I wasn't really referring to my posts, but all the other reactions I've seen. From what I've read, whenever anyone has criticised Frequency Therapeutics, it's been met with a pretty hardline defence of the company, even though they bring these criticisms on themselves, in my opinion.

I've noticed this across the web in my discussions with people about Frequency Therapeutics, and prior to their Phase 2a failure I was probably guilty of it too. I think it happens because people get emotionally invested in the company. They read up on what the company's doing and realize that in a few years maybe they'll be cured of tinnitus and have good hearing again. When someone questions or challenges the company, I think on a subconscious level there's resistance to it because it's tearing down that dream. It's hard to be unbiased about something when you're directly affected.

 

[Ehren M]

Apparently they are contacting patients who didn't get into previous trials that their next trial is about to start (source: people on Facebook).

Good. From the small bit of attention I've paid to this thread lately, it seems like their sample sizes tend to be smaller than we might all hope for. We need a healthy balance of selectivity and inclusiveness of participants. It's certainly not an easy task, and my heart goes out to those poor clinical statisticians trying to draw meaningful conclusions from subjective data reported by cantankerous Homo sapiens.

 

[Pete88]

I've noticed this across the web in my discussions with people about Frequency Therapeutics, and prior to their Phase 2a failure I was probably guilty of it too. I think it happens because people get emotionally invested in the company. They read up on what the company's doing and realize that in a few years maybe they'll be cured of tinnitus and have good hearing again. When someone questions or challenges the company, I think on a subconscious level there's resistance to it because it's tearing down that dream. It's hard to be unbiased about something when you're directly affected.

Agreed. At least prior to the Phase 2a results, all the available evidence looked very favorable. Coming out against it was more based in pessimism.

Now they have single dose studies that can't live up to the assumptions set by the safety study.

 

[Amv]

Probably I am wrong, but I really believe our solution to tinnitus comes more from neuromodulation than from hearing regeneration. I hope I am wrong!

 

[Jurger]

Agreed. At least prior to the Phase 2a results, all the available evidence looked very favorable. Coming out against it was more based in pessimism.

Now they have single dose studies that can't live up to the assumptions set by the safety study.

I disagree. In Phase 1/2 the drug didn't result in PTA improvements and WR scores improved marginally in about 35% of patients. Frequency Therapeutics didn't even talk about WR until after the results of Phase 1/2. I wasn't impressed after Phase 1/2, and for good reason.

 

[Justin Mills]

Probably I am wrong, but I really believe our solution to tinnitus comes more from neuromodulation than from hearing regeneration. I hope I am wrong!

That's not right, no. Tinnitus is usually from damage to hearing, so having a drug that can regenerate the damage would treat the underlying cause of tinnitus AND would also improve hearing perception and clarity. It would also address such issues as hyperacusis that again are caused by the structural damage.

My concern with FX-322 is that is focuses just on restoring the hearing hair cells. But we know that greater damage occurs to the synapses. I wonder why none of these companies try a two pronged approach. Like using the hair regeneration drug plus a drug that regenerates synapses like OTO-413 and PIPE-505. Maybe with this kind of more aggressive approach using two medications instead of one we would see clear results.