Frequency Therapeutics — Hearing Loss Regeneration

Let's first be able to scan cochleas and be able to analyse images of what's inside...

 

Additionally, FX-322 IS a public company (why drug companies can get a stock ticker without a proven drug is a mystery to me) so there is the specter of conflict of interest on the one hand and SEC accountability on the other.

Also, if there were another similar treatment with the kind of results that people were hoping for here, this thread would have gone completely silent. Activity is clustered here and 600+ pages long because we put all our eggs in whatever seems is the most promising basket at the time. Yesterday, Lenire. Today, FX-322, tomorrow, something else. Lather, rinse, repeat.

Everyone other than those with a strong stock position in FREQ will drop this thread like a hot potato the moment the next new shiny thing comes around. It helps keep things in perspective for me when I see tempers flare and wagons circle.

 

To anyone curious:

In my opinion, I think it's unclear to conclude much regarding the side effects. The problem is that the sample sizes in each group are small and obviously the patients are all different going in.

Any standard statistical test (like Fisher Exact Test, which they've used repeatedly) is not going to show any statistically significant difference between groups, with the only possible exception being that the placebo group saw no tinnitus side effects. However, this is meaningless because they say that there was a one-to-one correspondence between tinnitus pre-study and tinnitus post-study.

The only thing that is obvious is that four injections, each a week apart, creates a damaging environment. Fortunately, all side effects were transient. I wouldn't read too much into this aspect.

 

I wonder what the damage must have been. Poor the ones who participated in the trial. I can’t imagine being so desperate to enter a trial and come out with more damage!

 

You did mean this as a joke, right?

 

Indeed, zero multiplied by zero equals nothing. Tests throughout audiology are rudimentary.

Hearing damage vs hearing loss.

 

No it wasn't a joke. I was thinking if they can do liver, heart, hair, kidney, lung transplants, why can't they transplant hair cells in the 21st century?

I'm not a scientist, just a tinnitus sufferer trying to use his common sense.

So we can't scan and see the cochlea yet? Holy Jesus. I didn't even know that. We're so far from away from treatments.

 

I wonder what would be their excuse if severe hearing loss results fails... They will blame it on current delivery method

 

They'll just not include patients with severe hearing loss in the upcoming Phase 2.

 

Here's my opinion:

The ARHL trial (112) started in September, 2020. The Severe trial (113) started in November, 2020. According to Frequency Therapeutics in their May 13 Press Release, they had lead-in baselines for the ARHL trial:



So, logic says that if they learned their lesson in time for the ARHL trial, they should have also learned their lesson for the Severe trial.

All of this is to say that any placebo super responders will be highly damning. Assuming this isn't the case, if there is a lack of strong efficacy results, they will paint the following picture:

• Emphasis on "another safe trial."
• Their target audience was never severe patients, but those with moderate to moderately severe hearing loss and poor clarity issues.
• Highlight any super responders from the treatment group that seems encouraging.

Keep in mind that the Severe trial is broken down as N=30 participants, with 24 in treatment group and 6 in the placebo group. This is because it's primarily a Phase 1 safety trial; they are expanding the patient base and want as many different populations as possible to take the drug and achieve safety.

Designs like this (4:1 and small sample) are very difficult to prove groupwide statistical gains. Essentially, the treatment group has to utterly crush the placebos. If this occurs, there is a downside, which is that there are only 6 placebos, so it's not unfair to consider that maybe the placebo group, by chance, just wasn't a strong group.

My expectations from the Severe trial are to either walk away feeling the same as I do now or to feel dismayed by seeing weird placebo gains. I would feel more optimism if there was a nice group of super responders that landed in the treatment group only.

 

Why Frequency Therapeutics did NOT do a Phase 1 placebo-controlled study for moderate hearing loss cases? They did it as an open label. Why did they not also conduct a placebo control for the group that they initially believe has responded to the drug? Are they scared of something?

I mean, they know moderate hearing loss cases responded well to FX-322, but they decided to do full placebo controlled studies on AGE-RELATED HEARING LOSS, SEVERE HEARING LOSS RELATED, and skip the moderate hearing loss related?!

A confident company would have done an open label study for moderate hearing loss and ALSO a placebo-controlled study for the moderate hearing loss, so at least by now we would have been waiting for the upcoming results of severe hearing loss + moderate hearing loss studies.

Something doesn't smell right...

 

They included patients with moderate hearing loss in the original Phase 1/2. You answered your own question, "they know moderate hearing loss cases responded well to FX-322..." So, why spend a few million learning what you already know again? Seems like a huge waste of time/money for a company that can afford neither.

The severe and ARHL trials are intended as exploratory trials for inclusion to the future Phase 2. We know ARHL is out, but severe is TBD.

 

After 3 years, 4 trials and 150 people treated, it continues to be impossible to know if FX-322 works or not.

Apparently Frequency Therapeutics knew very quickly that Phase 2 was a fiasco.

And they shared very positive messages for months.

How can you choose to trust them? They clearly lied.

 

If any cohort responded "well" then the stock would not have tanked after the most recent botched trial. Point being that the existing trials in the books are, at best, inconclusive. There needs to be more concrete results and more repeatability.

 

And to add insult they posted and hired a Chief Manufacturing Officer!

 

Perhaps what you're missing is the different goals of Phase 1 vs Phase 2.

Phase 1 trials are powered poorly for efficacy and mostly intended for safety, with the additional exploratory goal of honing in on the ideal patient for Phase 2, a bona fide efficacy study.

It's just not true that a bunch of phase 1 trials equal one Phase 2 with large sample sizes.

The super responders in Phase 1/2 (if legit and not baseline deflators to get in) help them recruit for Phase 2. They were looking at ARHL and Severe SNHL to see what aspects of these arms could be considered for the next efficacy trial.

There's no getting around the fact that the drug has to succeed in the next Phase 2 at the group level (which doesn't mean everyone responds, just that enough people did to pull the group averages over the placebo averages).

Unfortunately, due to total incompetence, they probably didn't have lead in baselines before Phase 1/2 so even those results are at least slightly less trustworthy, even though low WR scores were not advertised at the time.

 

If what you are saying is true, that they "knew the Phase 2A was a fiasco," what incentive did they have to announce the interim readout in March as far back as September 2020 if they already knew, as you claim, that it was bad?

 

Is it a guess? If there is evidence, isn't it a breach of stock manipulation if they were lying? Have the legal proceedings actually been filed?

 

This is a very good question. They have no reason to have done this.

Do they really think the drug was working?

On the other hand, the CEO and other insiders only sell stocks, never buy, but whatever.

They had Phase 2A results at the latest around February 15, but continued to make false statements.

Day 90 reading is incomprehensible, I admit, but let's not forget that Frequency Therapeutics is a highly incompetent company.

 

I think you're fixated on the DRUG but not the TRIAL. They thought the TRIAL was working.

The CEO and Insiders had loads of options that had matured and were selling through a perfectly legal and "above board" practice. This is absolutely normal for any firm, there's an emotional investment in this firm on this forum, so everyone reacts to this news without considering the context. If you had options in the volume they do, you would also be motived to diversify your holdings?

Can you give examples of the false statements? Nowhere did they say the Phase 2A was a success. I see evidence of them making statements about the Phase 1/2 outcomes. The publishing of their work in the Otology journal. And, other various non-FX-322-specific hearing-loss commentary on their twitter. The only FALSE statement that frustrates me is that they indicated they would produce all Day-90 data at the interim readout, which they never did. And really, still haven't.

I don't know if you can blanket the entire company as highly incompetent, that's a lot of people that are invested in the development of PCA. They definitely sucked at developing the Phase 2A, it turns out. But, they've also EXPANDED their expertise in areas of hearing loss, audiology, trial design, and research. So, perhaps there's a few lessons learned to be applied to this next Phase 2.

 

I'm not questioning their scientists, I'm sure they're doing a good job.

- I agree that insider sales/purchases don't tell the whole story, but in the context of FREQ, it doesn't work in their favor.

- False statements, yes, when they reiterated how wonderful FX-322 was when they knew Phase 2A was a fiasco, I'd call it a false statement. Legally it s not, but their ultra positive attitude while Phase 2A was catastrophic makes me doubt.

I think we should all take a step back on FX-322, we have too little information to establish a reasoning.

I suppose the severe study will also be a fiasco, it will be necessary to wait for the second Phase 2 to have the definitive answer on whether it works or not.

Fortunately, this is not the only solution in the near future, other treatments, less wonderful of course, could help us.

 

I look forward to a detailed announcement of Phase 2a later this year. So far, only the number of occurrences of WR group level improvement of 10% or more has been announced. I hope that WR, WIN, PTA, the magnitude of changes at the individual level, and TFI etc. will be announced.

I think some people in the dosing group will observe the magnitude of the improvement, which is the real improvement plus the forged improvement.

 

CEO gets to buy shares at $0.61...

 

It's for this very reason that they should have done a placebo-controlled Phase 1 for moderate hearing loss.

It was their chance to prove their claim, regardless if it costs money or time...

This is a public company... and the public have the right to this.

Instead of going out tweeting thanking the candidates and doctors for their time conducting Phase 2a, GO OUT AND APOLOGIZE FOR YOUR ERRORS AND GROSS NEGLIGENCE...

 

For the severe hearing loss trials to have positive outcomes and pass their Phase, what happens if only one of the outcomes are positive e.g., shows audiogram improvements but no word score improvements?

 

For heaven's sake does FX-322 work or not! I have read 600 pages of this thread and I still don't understand.

 

I can't objectively praise management through the roof. Two decisions that make no sense:

1) Lack of lead-in WR scores.
2) Spacing 4 injections exactly 1 week apart. This was most certainly not a scientific choice.

The science hasn't crossed the finish line, but has pleased me enough thus far, given what they are up against.

 

Multi-dosing: No.
Audiograms: No.
Speech improvements for the right patient: Maybe.

 

With audiograms, the Phase 1 trials showed that they had improvements at the highest frequency that was tested which was 8 kHz and I think it was 4 patients that had improvements. If they had tested between 8-20 kHz then maybe most of the patients did have improvements in their audiograms.

Hopefully with the Phase 2 redo trials it shows improvement in the high to mid frequencies in the audiogram.

 

Excellent summary