Frequency Therapeutics — Hearing Loss Regeneration

[Ruse]

I wonder how much this will eventually cost, surely they will go for mass market?

Have they ever talked about pricing (in a general sense)?

 

[JohnAdams]

I wonder how much this will eventually cost, surely they will go for mass market?

Have they ever talked about pricing (in a general sense)?

$322

 

[Ringeee]

I don't know if my tinnitus is related to hearing loss, but I hope FX-322 comes out soon.

 

[Mr Mister]

IPOing now gives more value to investors since the increased value of the stock would be "priced in" after phase 2.

It's counterintuitive, but you may get a lot more funding by getting a wave of speculative investors now and a second wave of more conservative after phase 2. It's not that unusual for biotech startups to IPO at this early stage, some make it to market with a successful drug and some don't. I am not aware of a single biotech (even with very successful outcomes) that increased 10x value after phase 2 but it might in the time from phase 1 to FDA approval. Did you have an example in mind?

There is no reason to believe that Frequency doesn't believe in the drug based on IPO timing imo and there is certainly evidence that Astellas does believe in it.

Can you explain why you think an IPO would slow development?

You can think yourself how much would you be prepared to pay for Frequency Therapeutics share in two scenarios: 1) Drug is safe, 2) Drug is safe and effective at curing hearing loss. Scenario 1 is interesting and scenario 2 is one of the biggest breakthroughs ever in medicine.

Like I said IPO is a heavy process to any organisation let alone for a start-up with a staff of 20 people and takes a lot of time and resources. I am sure they manage to IPO the business but I would rather see them focussing all resources on completing phase 2 as fast as possible.

 

[JohnAdams]

but I would rather see them focussing all resources on completing phase 2 as fast as possible

Too bad. Ain't happening unless the government gets involved and incentivizes that.

 

[FGG]

You can think yourself how much would you be prepared to pay for Frequency Therapeutics share in two scenarios: 1) Drug is safe, 2) Drug is safe and effective at curing hearing loss. Scenario 1 is interesting and scenario 2 is one of the biggest breakthroughs ever in medicine.

Like I said IPO is a heavy process to any organisation let alone for a start-up with a staff of 20 people and takes a lot of time and resources. I am sure they manage to IPO the business but I would rather see them focussing all resources on completing phase 2 as fast as possible.

Their phase 2 is scheduled to end second half 2020. This puts them at faster than most. FDA approval is unfortunately always a slow process. I am very interested to see if Astellas can get (non-US) worldwide approval of FX-322 faster since they are funding that entire process now, including ex-US trials.

 

[Ringeee]

Too bad. Ain't happening unless the government gets involved and incentivizes that.

I wish all of Washington has tinnitus so there was an incentive to fast track a cure.

 

[Lucifer]

Their phase 2 is scheduled to end second half 2020. This puts them at faster than most. FDA approval is unfortunately always a slow process. I am very interested to see if Astellas can get (non-US) worldwide approval of FX-322 faster since they are funding that entire process now, including ex-US trials.

I still think Audion/Regain is ahead of Frequency Therapeutics since I assume once they are done with Phase 2 they will go on to Phase 3 whereas Frequency Therapeutics might have to do Phase 2b and then Phase 3.

 

[FGG]

I still think Audion/Regain is ahead of Frequency Therapeutics since I assume once they are done with Phase 2 they will go on to Phase 3 whereas Frequency Therapeutics might have to do Phase 2b and then Phase 3.

This seems likely to me. I just hope it doesn't take Frequency a year just to enroll for phase 2b. Though if Regain works, without the loss of supporting cells being a long term issue, then it would obviously be less pressing.

 

[Fabrikat]

Their phase 2 is scheduled to end second half 2020.

This is going to be like watching paint dry and grass grow.

I wonder if there are any Tinnitus Talk members participating in these trials.

 

[Margus]

The question is does Frequency Therapeutics truly believe in FX-322? The IPO value of the business would be at least 10 times higher after completion of successful phase 2 so from financial perspective it doesn't make sense to IPO it on the verge of a presumed breakthrough. Current owners have deep pockets and they could easily finance phase 2 without an IPO. Development would be faster without all the burden that comes from added regulations and requirements of a public listing.

However, it is easy to see why they want to IPO the business now as there are so many uncertainties. No credible sign of efficacy, true safety remains untested as they need to increase dosing substantially in the next phase and drug delivery is an issue as they claim the drug did not reach inner cochlea. Positive part is that following their development is quite interesting and with public listing they are required to provide more information and more frequently to the public.

Exactly my thoughts when I read news about the IPO. Frequency Therapeutics just had two rounds of funding, so clearly, they have enough money to fund further trials. Also, Astellas deal will inject more money if next trials prove to be successful. So why would one go IPO now, unless you suspect that it might not be a cure at the end. IPO will fill coffers of owners and first round investors regardless of the trial success. Especially in current market condition with so much money looking to be invested.

 

[Coleoptere]

If Audion/Regain is quicker it demonstrates that the FDA system is failing. Actually it then would have been better to follow the European route for Frequency. But let's see & dream on...

 

[ajc]

Is anyone going to the AAO-HNSF 2019 annual meeting?

https://plan.core-apps.com/aao2019/event/d29afee0ef623a96e8827526a952c271

Frequency Therapeutics' session is TODAY!!!

Session: Late Breaking Scientific Oral Presentations
Location: Ernest N. Morial Convention Center, Room 286/287
Date: Tuesday, Sep 17 8:24 AM
Duration: 5 minutes

 

[JohnAdams]

Frequency Therapeutics' session is TODAY!!!

I thought it was tomorrow? Today is better. If that's right then it already happened.

 

[ajc]

I thought it was tomorrow? Today is better. If that's right then it already happened.

Yes it already happened I guess? Will McLean from Frequency Therapeutics was part of the panel speaking.

They published the abstract study results, it is no longer locked (but it says final results are still to come...):
https://plan.core-apps.com/aao2019/abstract/b4e7cea55da7a6eeaa1e4abfb14e7c86

Authors: S King1, C LeBel2, W McLean2, J Herby2, C Runge3, R Gifford4, D Lee5, S King1
Institution: 1N/A, San Antonio, TX, 2Frequency Therapeutics, Woburn, MA, 3Medical College of Wisconsin, Milwaukee, WI, 4Vanderbilt University Medical Center, Nashville, TN, 5Mass Eye and Ear Infirmary - Dept of OTO, Boston, MA
Background:
Study Objectives:
Although most species can regenerate hair cells, hair cell loss in mammals is permanent because the subset of supporting cells that serve as hair cell progenitors during development fail to divide and differentiate on their own. This work showed that two small molecules that now comprise FX322 restore the regenerative potential of mouse and human progenitor cells in vitro and regenerate hair cells when applied to ototoxin damaged mouse tissue. Importantly, a single intratympanic injection of FX322 restores hair cells and auditory function in mice with trauma within one month after treatment. Utilizing small molecules to regenerate hair cells could provide a therapeutic advantage over the complexities and challenges associated with gene and cell therapies. This preclinical body of data supported the start of the first clinical trial of FX322 in patients with sensorineural hearing loss.

Methods:
The trial was conducted at three private US otolaryngology practices to assess the systemic safety, plasma PK, and effects on otoscopy, audiometry, and word testing of locally-delivered FX322. The trial was double-blinded, placebo-controlled and enrolled 23 patients with medical histories consistent with either noise-induced hearing loss or sudden sensorineural hearing loss which was considered stable (no change ≥10dB at any frequency, ≥6 months, PTA ≤70dB). Patients were randomized to either placebo or FX322 at two different dose volumes, and treatment was given as a single intratympanic dose. Patients were monitored overnight for safety and PK, and returned at months 0.5, 1, 2 and 3 for otoscopy, audiometry and word testing.

Results: As of the date of this writing the study remains blinded and final results will be presented at the annual AAO-HNS meeting.

 

[Ringeee]

Are we excited because restoring hearing loss could fix tinnitus? Have the people behind FX-322 made any comments in this treating tinnitus?

 

[JohnAdams]

Have the people behind FX-322 made any comments in this treating tinnitus?

Only a Reddit post from co-inventor of the drug FX-322 Will McLean under the username "The Leviathan" in which he expresses his optimism that restoring hearing will treat tinnitus.

 

[ajc]

Only a Reddit post from co-inventor of the drug FX-322 Will McLean under the username "The Leviathan" in which he expresses his optimism that restoring hearing will treat tinnitus.

The-Leviathan (aka suspected Will McLean) said:

"Also an ear expert here, and Ph.D. student in the above mentioned lab. Ultimately tinnitus comes down to hair cell damage/malfunction. Hearing loss might not be detected in people with tinnitus if the region responsible is small, and the nearby areas are excited by the traveling wave along the cochlea. Some ways to detect this are tone-matching experiments, and masking nearby regions. Either way, the fault lies in the hair cell, and regenerating or repairing those hair cells will help tinnitus. After all, the tinnitus is really just the brain filling in lost information not being relayed by hair cells"

 

[FGG]

Are we excited because restoring hearing loss could fix tinnitus? Have the people behind FX-322 made any comments in this treating tinnitus?

Tinnitus Handicap Index and loudness scale are also something they are measuring in phase 2 so they likely see an indication there.

 

[JohnAdams]

Tinnitus Handicap Index and loudness scale are also something they are measuring in phase 2 so they likely see an indication there.

Sauce please.

 

[ajc]

Sauce please.

https://www.sec.gov/Archives/edgar/data/1703647/000119312519239976/d72917ds1.htm

Planned Phase 2a clinical trial

Based on our analysis of the data from our Phase 1/2 clinical trial, we intend to initiate a randomized, double-blind, placebo-controlled, single- and repeat-dose Phase 2a clinical trial of FX-322 at approximately 12 sites in the United States in the fourth quarter of 2019. We plan to enroll approximately 96 adults aged 18 to 65 with stable SNHL. As in the Phase 1/2 clinical trial, patients must have a documented medical history consistent with either stable NIHL or stable SSNHL, with an average range of 26 to 70 dB loss measured by pure tone audiometry across four frequencies.

To explore how a single dose compares to multiple doses of FX-322, we plan to randomize patients to one of four groups, each of which will receive four injections, once per week at weekly intervals starting at the initial visit. Group 1 will receive one injection of FX-322 and three injections of placebo. Group two will receive two injections of FX-322 and two injections of placebo. Group three will receive four injections of FX-322. Group four will receive four injections of placebo. Patients will have follow-up visits two weeks after dosing and then monthly for seven months. The efficacy endpoints of this trial are expected to be WR, WIN, and pure tone audiometry in the range of 250 to 8000 Hz. The exploratory efficacy endpoints are expected to be the Tinnitus Functional Index, the Hearing Handicap Inventory for Adults, and pure tone audiometry in the range of 9000 to 16000 Hz. The selection of the efficacy endpoints in this study build on the learnings from the Phase 1/2 trial, and we believe will add to our knowledge on the potential ways in which FX-322 may improve hearing function. We expect to report top-line data from this trial in the second half of 2020. We may also conduct clinical research in presbycusis.

 

[FGG]

https://www.sec.gov/Archives/edgar/data/1703647/000119312519239976/d72917ds1.htm

Planned Phase 2a clinical trial

Based on our analysis of the data from our Phase 1/2 clinical trial, we intend to initiate a randomized, double-blind, placebo-controlled, single- and repeat-dose Phase 2a clinical trial of FX-322 at approximately 12 sites in the United States in the fourth quarter of 2019. We plan to enroll approximately 96 adults aged 18 to 65 with stable SNHL. As in the Phase 1/2 clinical trial, patients must have a documented medical history consistent with either stable NIHL or stable SSNHL, with an average range of 26 to 70 dB loss measured by pure tone audiometry across four frequencies.

To explore how a single dose compares to multiple doses of FX-322, we plan to randomize patients to one of four groups, each of which will receive four injections, once per week at weekly intervals starting at the initial visit. Group 1 will receive one injection of FX-322 and three injections of placebo. Group two will receive two injections of FX-322 and two injections of placebo. Group three will receive four injections of FX-322. Group four will receive four injections of placebo. Patients will have follow-up visits two weeks after dosing and then monthly for seven months. The efficacy endpoints of this trial are expected to be WR, WIN, and pure tone audiometry in the range of 250 to 8000 Hz. The exploratory efficacy endpoints are expected to be the Tinnitus Functional Index, the Hearing Handicap Inventory for Adults, and pure tone audiometry in the range of 9000 to 16000 Hz. The selection of the efficacy endpoints in this study build on the learnings from the Phase 1/2 trial, and we believe will add to our knowledge on the potential ways in which FX-322 may improve hearing function. We expect to report top-line data from this trial in the second half of 2020. We may also conduct clinical research in presbycusis.

Thanks for the correction. Tinnitus Functional Index and Hearing Handicap.

 

[JohnAdams]

https://www.sec.gov/Archives/edgar/data/1703647/000119312519239976/d72917ds1.htm

Planned Phase 2a clinical trial

Based on our analysis of the data from our Phase 1/2 clinical trial, we intend to initiate a randomized, double-blind, placebo-controlled, single- and repeat-dose Phase 2a clinical trial of FX-322 at approximately 12 sites in the United States in the fourth quarter of 2019. We plan to enroll approximately 96 adults aged 18 to 65 with stable SNHL. As in the Phase 1/2 clinical trial, patients must have a documented medical history consistent with either stable NIHL or stable SSNHL, with an average range of 26 to 70 dB loss measured by pure tone audiometry across four frequencies.

To explore how a single dose compares to multiple doses of FX-322, we plan to randomize patients to one of four groups, each of which will receive four injections, once per week at weekly intervals starting at the initial visit. Group 1 will receive one injection of FX-322 and three injections of placebo. Group two will receive two injections of FX-322 and two injections of placebo. Group three will receive four injections of FX-322. Group four will receive four injections of placebo. Patients will have follow-up visits two weeks after dosing and then monthly for seven months. The efficacy endpoints of this trial are expected to be WR, WIN, and pure tone audiometry in the range of 250 to 8000 Hz. The exploratory efficacy endpoints are expected to be the Tinnitus Functional Index, the Hearing Handicap Inventory for Adults, and pure tone audiometry in the range of 9000 to 16000 Hz. The selection of the efficacy endpoints in this study build on the learnings from the Phase 1/2 trial, and we believe will add to our knowledge on the potential ways in which FX-322 may improve hearing function. We expect to report top-line data from this trial in the second half of 2020. We may also conduct clinical research in presbycusis.

That's true sauce.

So now we at least know that we will potentially have an answer about tinnitus, in a year or so...

drug delivery is an issue as they claim the drug did not reach inner cochlea

I think you mean that it didn't improve low frequency audiogram scores. Remember it was only one small dose.

 

[Lucifer]

The report that @ajc provided, is that what was announced in Frequency's presentation?

Well if it is, it's good that they are measuring tinnitus this time round.

No mention of nerves growing and reattaching though.

 

[JohnAdams]

No mention of nerves growing and reattaching though.

That is because there is no way to measure that in vivo in humans. MRI's cannot see that. The only way to see that is to view it in dissected rodents. You cannot do that in humans because this is not Joseph Mengele's happy time human experiment game. If hearing is restored and tinnitus diminishes then we can only assume that happened.

 

[Lucifer]

I wonder if there are any Tinnitus Talk members participating in these trials.

A mutual friend of @síocháin was in the Regain trial who reported that his tinnitus and hyperacusis were much better and was able to play in his band again and go on tour.

I'm waiting for @síocháin's reply to see if she can get that person to come on Tinnitus Talk and talk about the trial and the improvements he got with Regain.

 

[Daniel Lion]

A mutual friend of @síocháin was in the Regain trial who reported that his tinnitus and hyperacusis were much better and was able to play in his band again and go on tour.

I'm waiting for @síocháin's reply to see if she can get that person to come on Tinnitus Talk and talk about the trial and the improvements he got with Regain.

Yeah, this person has disappeared or never existed... but good luck on your quest.

Weird question for everybody... let's say you took part in the next trial and were in the placebo group... would Frequency Therapeutics let you have the drug after seven months? In other words do the placebo patients get access to the drug, or do they have to wait like everybody else for the public release?

How does that work in trials? I have no idea... thanks.

 

[Mr Mister]

Did I miss that claim? Any source? Or is it our speculation?

This is what it says in the IPO document: "The drug diffuses into the cochlea and is expected to create the greatest concentration of drug in the high frequency region of the cochlea."

Frequency Therapeutics tested hearing up to 8000 Hz in the clinical trials. Some people on this site suggest there was no impact on audiogram because the drug did not reach inner cochlea where lower frequencies are located. If that is the case then there is a problem with drug delivery. Maybe you have to stand on your head for two days to make it work

 

[JohnAdams]

Maybe you have to stand on your head for two days to make it work

After injection:

 

[Coleoptere]

Maybe you have to stand on your head for two days to make it work

If that is what it takes... I'm willing to do so. But it will be a touch challenge though!