Frequency Therapeutics — Hearing Loss Regeneration

[Keith Handy]

I am reading a lot into this part:

Will develop strategies to turn laboratory and clinical observations into new, increasingly sensitive diagnostic methodologies...

In particular, "laboratory and clinical observations" sounds like a carefully worded way of saying "data we can't formally report due to flawed studies, but from which we are (hopefully) gleaning something which will point us in the right direction."

I maintain hope. Patience is the tricky part.

 

[Diesel]

I am reading a lot into this part:

In particular, "laboratory and clinical observations" sounds like a carefully worded way of saying "data we can't formally report due to flawed studies, but from which we are (hopefully) gleaning something which will point us in the right direction."

I maintain hope. Patience is the tricky part.

Agree. To paraphrase Lucchino, "this is a trial problem, not a problem with FX-322." The hiring of Lichtenhan and the wording of the release reinforces his comments and is an indication the focus is on challenges not directly related to the development of the drug itself.

It's not a matter whether it "works or not," it's "how well" and for "whom specifically."

Interesting development.

 

[GlennS]

To paraphrase Lucchino, "this is a trial problem, not a problem with FX-322."

I wouldn't expect them to say anything different regardless of the underlying reality.

The company's job is to ride this pony as far as they can.

 

[Zugzug]

So many ideas we've been talking about are underlying this hire.

• Making sense of the truth behind super responders.
• Science works in vitro and probably somehow does something in vivo, but incremental change has to be accepted. Current diagnostics aren't ideal for this.

In my opinion, this is totally the way to go. Double down on novelty and focus on incremental change. I will give them credit for a smart move.

 

[RB2014]

Agree. To paraphrase Lucchino, "this is a trial problem, not a problem with FX-322." The hiring of Lichtenhan and the wording of the release reinforces his comments and is an indication the focus is on challenges not directly related to the development of the drug itself.

It's not a matter whether it "works or not," it's "how well" and for "whom specifically."

Interesting development.

I'm not sure I believe that it was completely a trial problem. The non placebo group should have had some hearing restored if it worked like they intended and on average more/improved word scores than the non placebo group. They really need to figure out why it isn't working as they had hoped. Hopefully the new hire does that...

 

[just1morething]

Agree. To paraphrase Lucchino, "this is a trial problem, not a problem with FX-322." The hiring of Lichtenhan and the wording of the release reinforces his comments and is an indication the focus is on challenges not directly related to the development of the drug itself.

It's not a matter whether it "works or not," it's "how well" and for "whom specifically."

Interesting development.

If true, the stock price of FREQ would reflect that. Look at all the shares the directors of the company received by going public. Smart people are not always honest and many of them are greedy.

 

[Diesel]

I'm not sure I believe that it was completely a trial problem. The non placebo group should have had some hearing restored if it worked like they intended and on average more/improved word scores than the non placebo group. They really need to figure out why it isn't working as they had hoped.

Do you mean the Phase 2A which seemed to have participants that didn't have word score deficits at entry, but then performed better under placebo? And that we haven't seen any clear data on?

This hire seems to be directly related to "figuring out why it isn't working as they had hoped."

 

[Zugzug]

I'm not sure I believe that it was completely a trial problem. The non placebo group should have had some hearing restored if it worked like they intended and on average more/improved word scores than the non placebo group. They really need to figure out why it isn't working as they had hoped.

I agree with you that it wasn't a trial problem in the sense of cheaters ruining everything. I believe the drug genuinely failed the task at hand in Phase 2.

Where I do think the trial was a problem was in the benchmarks set forth to demonstrate a revolutionary drug. This may sound weak, but PTA, WR, and SIN are kind of slam dunks for something that's never been done before. I have a vision of really simplifying this problem. It could delay the timeline, but I definitely think they should crawl before they walk when it comes to in vivo demonstrations.

Now, if there were already hearing regeneration drugs, the bar needs to be a lot higher. There is nothing. It's okay to go for strong proofs of incremental change, IMO.

 

[rei]

So many ideas we've been talking about are underlying this hire.

• Making sense of the truth behind super responders.
• Science works in vitro and probably somehow does something in vivo, but incremental change has to be accepted. Current diagnostics aren't ideal for this.

In my opinion, this is totally the way to go. Double down on novelty and focus on incremental change. I will give them credit for a smart move.

Yep, you guys are always right on the mark. That's why I'm on still on this forum and still reading this thread everyday. Thank you.

 

[Zugzug]

Yep, you guys are always right on the mark. That's why I'm on still on this forum and still reading this thread everyday. Thank you.

To be fully transparent and fair, my position on the super improvers is that something is going on. If it ends up being the drug, @Diesel and @FGG deserve more credit.

 

[FGG]

• Addition of Jeffery T. Lichtenhan, Ph.D., a leading expert in hearing diagnostics and measurement.
• Dr. Lichtenhan's laboratory has aimed to develop novel, clinically relevant measures of auditory dysfunction.
  
• Will help to advance the Company's hearing clinical development programs, including its lead program, FX-322.
• Will develop strategies to turn laboratory and clinical observations into new, increasingly sensitive diagnostic methodologies to support development of new therapeutics for acquired sensorineural hearing loss.
• Frequency continues to build out its hearing research and development efforts, while working to define specific patient populations where its lead treatment candidate, FX-322, may have the greatest impact.

Reading through his publications, he wrote a book a few years ago on new ways to use Electrocochleography (ECochG) data. This was mentioned in a description of the book:

"A major long-term goal of ECochG is to help differentiate outer hair cell (OHC) from inner hair cell (IHC) or presynaptic losses..."

He's also an author on this publication:

https://scholar.google.com/scholar?hl=en&as_sdt=0,34&as_vis=1&q=Jeffery+T.+Lichtenhan&btnG=#d=gs_qabs&u=#p=sAKJs2geZm0J

Anyone know the difference between DPOAEs and SFOAEs?

 

[Chad Lawton]

I'm not sure I believe that it was completely a trial problem. The non placebo group should have had some hearing restored if it worked like they intended and on average more/improved word scores than the non placebo group. They really need to figure out why it isn't working as they had hoped. Hopefully the new hire does that...

How do you think baking a cake would turn out if you opened the oven every 5 minutes and put another cracked egg and cup of flower in the mix? They shot 4 injections into the ear which was a combination of drug/placebo and it didn't work and jacked up the chemistry of the ear but we have 2 separate trials showing us a single injection works.

 

[Forsberg]

I had quite big hopes for the Phase 2a. To be honest FX-322 is the last thing I am waiting for. If it fails, then I fail too. Tinnitus is too heavy to carry all the time without any serious hope, and potentially for 40 years ahead...

 

[FGG]

How do you think baking a cake would turn out if you opened the oven every 5 minutes and put another cracked egg and cup of flower in the mix? They shot 4 injections into the ear which was a combination of drug/placebo and it didn't work and jacked up the chemistry of the ear but we have 2 separate trials showing us a single injection works.

I love this because it really is a great analogy.

If you bake a cake and get something even slightly wrong, you can ruin the whole cake and then you need to try again after you tweak the recipe (this is why cooking is *way* more fun than baking btw...).

Both baking and some medicine are really precision chemistry, change one step and you change the outcome.

 

[Diesel]

How do you think baking a cake would turn out if you opened the oven every 5 minutes and put another cracked egg and cup of flower in the mix? They shot 4 injections into the ear which was a combination of drug/placebo and it didn't work and jacked up the chemistry of the ear but we have 2 separate trials showing us a single injection works.

I like this analogy.

 

[Keith Handy]

I love this because it really is a great analogy.

If you bake a cake and get something even slightly wrong, you can ruin the whole cake and then you need to try again after you tweak the recipe (this is why cooking is *way* more fun than baking btw...).

Both baking and some medicine are really precision chemistry, change one step and you change the outcome.

The cake analogy and the "if you can't accept me at this" meme from several weeks ago (with the hair cells) might be my two favorite things in this thread.

 

[RB2014]

How do you think baking a cake would turn out if you opened the oven every 5 minutes and put another cracked egg and cup of flower in the mix? They shot 4 injections into the ear which was a combination of drug/placebo and it didn't work and jacked up the chemistry of the ear but we have 2 separate trials showing us a single injection works.

If it worked, the guy that got 4 FX-322 injections should have gotten some benefit from the drug and it would have showed up in his audiograms and word scores. Or the guy that got 3 FX-322 injections and then the placebo injection last. Or the guy that got a placebo injection and then 3 FX-322 injections... or the guy that got 3 placebo injections and then 1 FX-322 injection at the end.

There is something else going on that they are not understanding. You can't just blame the trial procedure entirely.

 

[Guywithapug]

How do you think baking a cake would turn out if you opened the oven every 5 minutes and put another cracked egg and cup of flower in the mix? They shot 4 injections into the ear which was a combination of drug/placebo and it didn't work and jacked up the chemistry of the ear but we have 2 separate trials showing us a single injection works.

Maybe instead of Langer they should have consulted Emeril fucking Lagasse...

"1 part CHIR99021 to 2 parts valproic acid. You want to make sure to get the proper temperature before basting the cochlea, otherwise the hairs will not rise"

 

[Street Novelist]

I had quite big hopes for the Phase 2a. To be honest FX-322 is the last thing I am waiting for. If it fails, then I fail too. Tinnitus is too heavy to carry all the time without any serious hope, and potentially for 40 years ahead...

I still believe the drug works. They just screwed up with mixing the drug with the placebo. One injection of FX-322 should get results. The only question is how far into the cochlea does it go and do subsequent shots, dosed far apart, deliver greater results.

 

[FGG]

If it worked, the guy that got 4 FX-322 injections should have gotten some benefit from the drug and it would have showed up in his audiograms and word scores. Or the guy that got 3 FX-322 injections and then the placebo injection last. Or the guy that got a placebo injection and then 3 FX-322 injections... or the guy that got 3 placebo injections and then 1 FX-322 injection at the end.

There is something else going on that they are not understanding. You can't just blame the trial procedure entirely.

I think you are oversimplifying it.

They did report some word score benefit. It was just dampened compared to the single dose results. They have said that 4 weekly shots was problematic period (fluid or pressure effect?) whether you got placebo or drug and there was an additional additive effect (biochemical? formulation effect?) for more drug.

Complicating that, there were placebo (and Phase 2a drug) responders who were found to have artificially decreased their baseline word scores.

This is why they are saying it's a trial fault: multi-dosing ("adding more eggs while the cake is cooking") and recruiting that favored word score depression (the amount of genuine patients that fit their very specific audiologic criteria of low word scores but above serious PTA is low) are both trial design failures.

 

[VeryUnfortunate]

Okay so I have been keeping up with this thread since the onset of my tinnitus, and I was disappointed by the recent results from their multiple injection trial.

However I don't remember reading anywhere of them specifically mentioning the treatment's effect on tinnitus.

Does anyone know if they released some concrete information on the most recent trial's effect on tinnitus?

I know it's only a secondary measure and that they said they were issues with the delivery method, but I don't remember them specifically mentioning tinnitus in their 90 day readout. So for all we know it might still help with tinnitus?

 

[kiki]

The largest shareholder of FREQ has changed.

On March 31, Federated Global Investment Management Corp increased the number of shares acquired by 170%.

https://money.cnn.com/quote/shareholders/shareholders.html?symb=FREQ&subView=institutional

I don't know what kind of fund this fund is.

However, with such a large investment, I would like to believe that this fund has invested in FREQ because it is worth it.

 

[FGG]

Okay so I have been keeping up with this thread since the onset of my tinnitus, and I was disappointed by the recent results from their multiple injection trial.

However I don't remember reading anywhere of them specifically mentioning the treatment's effect on tinnitus.

Does anyone know if they released some concrete information on the most recent trial's effect on tinnitus?

I know it's only a secondary measure and that they said they were issues with the delivery method, but I don't remember them specifically mentioning tinnitus in their 90 day readout. So for all we know it might still help with tinnitus?

Not yet. Hopefully they will with full results.

 

[r34d1ng]

FREQ's presentation at the 20th Annual Needham Virtual Healthcare Conference starts in 30 minutes.

Live streaming is available here.

 

[r34d1ng]

Next steps for FX-322:

They insisted on the fact that Phase 2a trial design introduced bias, and that four successive injections didn't create the best environment in the inner ear for FX-322's regenerative properties. Future trials will be single-dose. This does not rule out the possibility to inject FX-322 multiple times, but it won't be on a weekly basis.

Lucchino was quite confident and said the company is focused on gathering more information from ongoing trials to eventually advance to a Phase 3.

By the way, more information on their multiple sclerosis drug later this year.

 

[Lukee]

The largest shareholder of FREQ has changed.

On March 31, Federated Global Investment Management Corp increased the number of shares acquired by 170%.

https://money.cnn.com/quote/shareholders/shareholders.html?symb=FREQ&subView=institutional

I don't know what kind of fund this fund is.

However, with such a large investment, I would like to believe that this fund has invested in FREQ because it is worth it.

Kiki is right. BlackRock also took a huge share at a discount. They must believe that FREQ is worth something to take that kind of position. The flip side of it is a pump and dump, which commonly happens when breakout stocks miss their target, so we have to be careful/mindful of that.

 

[FGG]

The largest shareholder of FREQ has changed.

On March 31, Federated Global Investment Management Corp increased the number of shares acquired by 170%.

https://money.cnn.com/quote/shareholders/shareholders.html?symb=FREQ&subView=institutional

I don't know what kind of fund this fund is.

However, with such a large investment, I would like to believe that this fund has invested in FREQ because it is worth it.

From a quick reading, Federated Global invests $30 billion in funds for 49 clients. $177 million is less than 1% of their portfolio. They also don't appear to be focused on biotech the way some other funds are.

Perceptive (who are focused on biotech) slightly added to their position. That's probably a better sign than the above imo if people want to use stock as an indicator (I don't like to personally).

 

[Diesel]

Interesting Q&A with Lucchino in the webinar today. Most important take-away from me was the question about the next FX-322 trials, and outlook for FX-322 as a single dose drug.

While he didn't clarify exactly what the next FX-322 trials would be, they did present that they are working with the FDA to kick off more studies 2H/2021.

Lucchino also commented, (paraphrasing) "If we had to position FX-322 as a product based on the single-dose studies today, we would go forward with a patient population that is 18-65 that shows at least a 10% improvement [with a single dose]. This is about a population of 10M -14M people (Americans)."

Based on that population estimate, that sounds to me that Lucchino is indicating that they are planning to identify FX-322 "1.0" to be intended for patients with Moderate -> Severe hearing loss.

It's likely then that a future Phase 1B / Phase 2 will be more patient focused on that Moderate -> Severe range.

----

Lucchino also re-iterated that in the future, there could be multi-dose injections, but longer than weekly.

NOTE: Zero discussion on reformulation or changing FX-322 itself.

 

[FGG]

Next steps for FX-322:

View attachment 44541

They insisted on the fact that Phase 2a trial design introduced bias, and that four successive injections didn't create the best environment in the inner ear for FX-322's regenerative properties. Future trials will be single-dose. This does not rule out the possibility to inject FX-322 multiple times, but it won't be on a weekly basis.

Lucchino was quite confident and said the company is focused on gathering more information from ongoing trials to eventually advance to a Phase 3.

By the way, more information on their multiple sclerosis drug later this year.

I'm glad future trials will include "lead in baselines" to mitigate the artificial baseline word score depression in the future.

 

[ColinUK]

But does it do anything for tinnitus...