Frequency Therapeutics — Hearing Loss Regeneration

I had this thought this morning after realizing the completion date for the age-related phase 1 trial is June 2021, insurance coverage may not be the primary motivation for adding this trial after all.

I suspect what might be going on is that they plan to add this cohort to an upcoming (pivotal) phase 2b/3.

It would make recruitment vastly easier and quicker.

I think the 90 day read out could also be to potentially prepare Astellas for the next trial. I do wonder when the "blinding" lifts and maybe this is a way for them to get an early read.
This actually makes a lot of sense. A pivotal phase or phase 3 can include randomized classes or sub-groups with controls (SNHL, NIHL, age-related, severe). Ultimately the outcomes to be measured across classes share the same metrics, so it could work. May shorten the length of the trial, too.

If the 90-day is an interim analysis, the subjects can remain blinded... only summary data would be made available, which may be enough. I imagine top-line improvements, if are anything like the Phase 1/2, may still be significant.
 
All of these press releases and announcements from Frequency Therapeutics lately sure seem encouraging. Despite my tinnitus of seven months not having improved much at all since it started in March, I don't spend much time on Tinnitus Talk other than to keep up with the research; this thread being the most viewed.

Big thanks to all who keep staying on top of the FX-322 news and contribute to this thread. I truly hope the Phase 2a results are favorable enough to get the ball really rolling on a (hopefully) quick release to market and finally having an actual cure for this monster.
 
This actually makes a lot of sense. A pivotal phase or phase 3 can include randomized classes or sub-groups with controls (SNHL, NIHL, age-related, severe). Ultimately the outcomes to be measured across classes share the same metrics, so it could work. May shorten the length of the trial, too.

If the 90-day is an interim analysis, the subjects can remain blinded... only summary data would be made available, which may be enough. I imagine top-line improvements, if are anything like the Phase 1/2, may still be significant.
Yes, I think they'll merge the various patient populations in a combined trial after Phase 2a is finished.
 
Question - would having a gel osmose into the cochlea increase inflammation?
 
There's been a lot of positive comments in a row as of late. Including some recent FX-322 'converts'... I'm gonna sit back while the skeptical doubters roll in...
 
A thought just hit me. I know some people have had trepidations about getting a high-frequency audiogram, or don't really have access to one. But, a poor man's way to test some of your high frequencies would be to use the Tinnitus Play app.

I use one of neuromodulation settings to mask some of my high-frequency hissing, but I just realized you could also use this setting to see if you can at least hear these frequencies in some capacity. For example, you can enter in 12 kHz, 13 kHz, 14 kHz etc, and on the neuromod setting the app plays beats at and around that frequency.

It's obviously not a perfect approximation of a true calibrated audiogram by any means, but I think it could serve as a quick and dirty way to suss out if you have any deep dips.
 
There's been a lot of positive comments in a row as of late. Including some recent FX-322 'converts'... I'm gonna sit back while the skeptical doubters roll in...
Announcing trials is one thing, delivering sustained, predictable improvement that's beneficial in day-to-day life is another. We're not out of the woods yet.
 
Frequency Therapeutics already does a pretty good job of that in their monthly presentation:

https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

It covers all of the basics, has illustrations, and is pretty easy to get through. Since it's put out by the company itself, it's also much less likely to contain false info or unwarranted speculation that could seep into any community-based fact sheet.
Yes, but I don't consider all their info being truthful... I don't want a fact sheet coming from them, nor illustrations... who verified them? I want to see a private 3rd party reviewing all their saying...

Because honestly whoever sees their presentation would really think they got the miracle drug.

My original idea was meant to compile major points and cross check them with verified facts...
 
Yes, but I don't consider all their info being truthful... I don't want a fact sheet coming from them, nor illustrations... who verified them? I want to see a private 3rd party reviewing all their saying...

Because honestly whoever sees their presentation would really think they got the miracle drug.

My original idea was meant to compile major points and cross check them with verified facts...
A publicly traded US firm is subject to SEC regulations that among many things, is required to be compliant with specific guidelines for any material used for marketing purposes, public consumption, or investor evaluations. Their website and all materials posted on the website must be compliant with these guidelines.

Typically a compliance officer who is registered with the SEC is required to review and approve all materials for public consumption to ensure they meet all regulatory guidelines. Generally, the guidelines call for the materials to be factual, based on factual sources, and do not speculate, imply, promise, or guarantee a result or outcome.

Should the firm violate these guidelines, the firm itself, its executives, or the compliance officer would be subject to an investigation. The SEC would announce this investigation. It would lead to a lawsuit. People do jail time. It would decimate Frequency Therapeutics' potential to increase its shareholder return, and do business effectively.

Bottom line: If it's on their site, it's the most accurate source available for their product.
 
Yes, but I don't consider all their info being truthful... I don't want a fact sheet coming from them, nor illustrations... who verified them? I want to see a private 3rd party reviewing all their saying...

Because honestly whoever sees their presentation would really think they got the miracle drug.

My original idea was meant to compile major points and cross check them with verified facts...
Clinical trials are not run by the companies themselves. The only way for the information to be falsified is if Frequency Therapeutics altered the results.

If so, that would be an Elizabeth Holmes/Theranos level of fraud and there is no evidence of that.

They are credible. Their C-suite have very long and good track records in the industry.

David Lucchino

And Carl LeBel was with Amgen for a decade or so before joining Frequency Therapeutics.

Jeff Karp and Robert Langer also both have very good research reputations.
 
Who will be funding Frequency Therapeutics' phase 3 trial if they are successful with phase 2? Will it be Astellas funding it/giving milestone payments? As far as I know, this would cost millions. Apologies if this has been answered.

@Greg Sacramento had suggested more issuing of shares/dilution to fund this, but what I heard was that Frequency Therapeutics wouldn't need to do this with the partnership with Astellas?
 
Who will be funding Frequency Therapeutics' phase 3 trial if they are successful with phase 2? Will it be Astellas funding it/giving milestone payments? As far as I know, this would cost millions. Apologies if this has been answered.

@Greg Sacramento had suggested more issuing of shares/dilution to fund this, but what I heard was that Frequency Therapeutics wouldn't need to do this with the partnership with Astellas?
According to their 10-K filing with the SEC, which I ENCOURAGE everyone who regulars this discussion to read, it provides significant detail on the operations of the business, their strategic plan, partnerships, agreements, financial disclosures:

https://investors.frequencytx.com/static-files/ba0fb3a0-c9c5-46e7-84fd-ad93e157759d

They get milestone payments from Astellas. Frequency Therapeutics also has enough cash to operate through the remaining phase.

PAGE 4:

Under our agreement with Astellas, Astellas is responsible for the development and commercialization of FX-322 outside of the United States. As consideration for the licensed rights under the Astellas Agreement, Astellas paid us an upfront payment of $80.0 million in July 2019 and has agreed to pay potential development milestone payments of up to $230.0 million. Specifically, we would receive development milestone payments of $65.0 million and $25.0 million upon the first dosing of a patient in a Phase 2b clinical trial for SNHL in Europe and Asia, respectively, and $100.0 million and $40.0 million upon the first dosing of a patient in a Phase 3 clinical trial for SNHL in Europe and Asia, respectively. If the Astellas licensed products are successfully commercialized, we would be eligible for up to $315.0 million in potential commercial milestone payments plus tiered royalties on any future product sales ranging from low- to mid-teen percentages.

PAGE 21: License and collaboration agreements

Astellas Pharma Inc. In July 2019, we entered into the Astellas Agreement with Astellas, under which we granted Astellas an exclusive, royalty-bearing, sub-licensable, nontransferable license to certain patent rights to research, develop, manufacture, have manufactured, use, seek and secure regulatory approval for, commercialize, offer for sale, sell, have sold and import, and otherwise exploit licensed products containing both a GSK-3 inhibitor and an HDAC inhibitor, or the Astellas licensed products, including our product candidate FX-322, outside of the United States. We also granted Astellas a right of first negotiation and a right of last refusal if we enter into any negotiation or agreement of any kind (other than an acquisition of all of our stock or assets) with any third party under which such third party would obtain the right to develop, manufacture, or commercialize Astellas licensed products in the United States. We and Astellas have agreed to jointly develop the Astellas licensed products, including carrying out joint studies. Each party has agreed to use commercially reasonable efforts to carry out development activities assigned to it under an agreed-upon development plan. Astellas has agreed to use commercially reasonable efforts to obtain regulatory approval for at least one Astellas licensed product in SNHL and in age-related hearing loss, in each case, in one major Asian country and one major European country. We have agreed to use commercially reasonable efforts to obtain regulatory approval for at least one Astellas licensed product in the United States. Astellas has the sole right to commercialize the Astellas licensed products outside of the United States, and we have the sole right to commercialize the Astellas licensed products in the United States. Astellas has agreed to use commercially reasonable efforts to commercialize Astellas licensed products in a major Asian country and a major European country following receipt of regulatory approval in such countries. As consideration for the licensed rights under the Astellas agreement, Astellas paid us an upfront payment of $80.0 million in July 2019 and has agreed to pay potential development milestone payments up to $230.0 million. Specifically, we would receive development milestone payments of $65.0 million and $25.0 million upon the first dosing of a patient in a Phase 2b clinical trial for SNHL in Europe and Asia, respectively, and $100.0 million and $40.0 million upon the first dosing of a patient in a Phase 3 clinical trial for SNHL in Europe and Asia, respectively. If the Astellas licensed products are successfully commercialized, we would be eligible for up to $315.0 million in potential commercial milestone payments and also tiered royalties at rates ranging from lowto mid-teen percentages. The Astellas Agreement remains in effect until the expiration of all royalty obligations. Royalties are paid on a licensed product-by-licensed product and country-by-country basis until the latest of (i) the expiration of the last valid claim in the licensed patent rights with respect to such Astellas licensed product in such country or (ii) a set number of years from the first commercial sale of such Astellas licensed product in such country. Astellas may terminate the Astellas Agreement at will upon 60 days' written notice. Each party has the right to terminate the Astellas Agreement due to the other party's material breach if such breach remains uncured for 90 days (or 45 days in the case of nonpayment) or if the other party becomes bankrupt.

PAGE 80: BALANCE SHEET

They ended 2019 with:

Cash, cash equivalents and short-term investments $217,355,000
 
Hmm, they wouldn't publish after 90 days if they didn't see something in the current trial... Trials for severe and age related hearing loss are also very positive indications.
The severe hearing loss treatment is plausible I'd think based off of the fact that there potentially is still sufficient support cells to regrow. The interesting question would actually be what is the difference between FX-322 and OTO-6XX in terms of treatment. OTO-6XX is apparently going to work with severe patients, however I wonder whether it uses a similar or a different method of instigating growth to FX-322.
 
Who will be funding Frequency Therapeutics' phase 3 trial if they are successful with phase 2? Will it be Astellas funding it/giving milestone payments? As far as I know, this would cost millions. Apologies if this has been answered.

@Greg Sacramento had suggested more issuing of shares/dilution to fund this, but what I heard was that Frequency Therapeutics wouldn't need to do this with the partnership with Astellas?
Astellas is seemingly funding part of the phase 3 trials through their milestone money. These trials being done in Asia and Europe are also recognised by the FDA.I think that there could be some more issuing of shares, however they have not reached full subscription yet from their current share allocation at present either.
 
Maybe they will just read out things we all already know but phrased differently?
We don't know anything about the Phase 2a, except the design of the trial. I assume the 90-day release will be a top-line readout. Which means they will show the baseline and 90-day aggregate result for each endpoint and each injection cohort compared to placebo.

EXAMPLE: (all at 90-days):
All would show injection vs placebo:

Word Score - Quiet: - 1-injection - 50%, 2-injection - 60%, 4 injection 80% (p-value 0.010)
Word Score - Noise: - 1-injection - 30%, 2-injection - 50%, 4 injection 70% (p-value 0.0x0)
Pure Tone Average: - 1-injection 10 dB improvement, 2-injection 20 dB, etc etc
TFI: 1-injection 10% reduction, 2-injection 20% reduction, etc etc


You get the idea... I would be delighted to see similar detail as the Phase 1/2 results; with hopefully some insight into audiogram improvements and breakouts into cohort improvements. However, I expect it to be a top-line summary of sorts; otherwise I don't see how it could be done without ublinding the trial.
 
I had this thought this morning after realizing the completion date for the age-related phase 1 trial is June 2021, insurance coverage may not be the primary motivation for adding this trial after all.

I suspect what might be going on is that they plan to add this cohort to an upcoming (pivotal) phase 2b/3.

It would make recruitment vastly easier and quicker.

I think the 90 day read out could also be to potentially prepare Astellas for the next trial. I do wonder when the "blinding" lifts and maybe this is a way for them to get an early read.
I think that this could be entirely accurate, although I also believe that Frequency Therapeutics will utilise the opportunity to demonstrate that FX-322 works with other cohorts and for more types of hearing loss too. Therefore this enables Frequency Therapeutics to demonstrate the efficacy of FX-322 more broadly.

I still hope that Frequency Therapeutics do push for compassionate use and also have good results too.
Maybe they will just read out things we all already know but phrased differently?
I definitely don't see the purpose in doing that. There could be the possibility where they are actually able to read out the results that they have achieved at day 90, however not remove the blinding to confirm or deny whether the improvement was from those obtaining FX-322.
This actually makes a lot of sense. A pivotal phase or phase 3 can include randomized classes or sub-groups with controls (SNHL, NIHL, age-related, severe). Ultimately the outcomes to be measured across classes share the same metrics, so it could work. May shorten the length of the trial, too.

If the 90-day is an interim analysis, the subjects can remain blinded... only summary data would be made available, which may be enough. I imagine top-line improvements, if are anything like the Phase 1/2, may still be significant.
I think that there would be no surprises if Frequency Therapeutics looked to shorten the trial if phase 2 results looked successful. In fact I would think that there is a very high likelihood that Frequency Therapeutics would be doing all they could to get a successful medicine out there as quickly as they can. Especially when ultimately there does not seem to be any real differences in the treatment required between the different cohorts. Consequently I think that the ability to use a broader range of candidates to fulfil phase 3 obligations would be almost certain to speed things up because by right it would largely eliminate the recruitment issues that Frequency Therapeutics had with the current trial.

Consequently I think that the outcome Frequency Therapeutics is going to be hoping for is to get better results across the board from the current trial and particularly in in the multiple dose group. Probably the biggest improvement that would be gained from the current trial is that there theoretically should be bigger improvement in the very high frequencies. Nevertheless the phase 2a results could end up being particularly significant for how FX-322 proceeds.
 
Clinical trials are not run by the companies themselves. The only way for the information to be falsified is if Frequency Therapeutics altered the results.

If so, that would be an Elizabeth Holmes/Theranos level of fraud and there is no evidence of that.

They are credible. Their C-suite have very long and good track records in the industry.

David Lucchino

And Carl LeBel was with Amgen for a decade or so before joining Frequency Therapeutics.

Jeff Karp and Robert Langer also both have very good research reputations.
Do you think FX-322 could be out next year, or in 2022?
 

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