Frequency Therapeutics — Hearing Loss Regeneration

I defer to others for good explanations of the differences, but a somewhat related aspect, the new Texas, USA stem cell law that went into effect on September 1, 2017 is a good example of how quickly things can change with regenerative medicine. With the stroke of a pen, the availability of treatments to patients (in Texas at least) was increased dramatically last month.

No more waiting for the results of long term double-blind studies, no more waiting 3 to 5 years for FDA approvals. If the doctors and patients feel something may help (within the regulations of the new law), now they can just go ahead and do it.

http://www.senate.state.tx.us/members/d07/press/en/p20170613a.pdf

 

What a loose statement.

See attachment; overall phase 1 to approval: 9.6%. Curious for your data.

 

Cool. Btw spirit flys to Dallas so just bring a small personal bag and get this procedure done there with only 400$ travel cost in 18' or 19'

 

I find it actually not that bad. What's funny is that audiology or ENT isn't even listed in the disease categories... If our category is in "Other", then the chances are 16% which is quite nice. They don't mention regenerative medecine either

 

For those interested; the investors behind seem to be through Clark Hill Partners and Latham and Watkins.
https://angel.co/frequency-therapeutics

Looking whether in there portfolio already some successful Biotech companies, but haven't found so far, only found Charles River in their network. Seems an interesting company.

 

When the first patient is supposed to take their medicne?

 

They said 12 to 18 months at last february. So I guess July to October 2018 that the time when they will start.
I am considering about going to trial but I am not living in US

 

Explain to me, please. The company "Frequency theraputics", as is known, conducts perspective developments on hearing treatment by activating "progenitor cells". The site says that their main focus is noise-induced hearing loss. Does this mean that they are not affected by other causes, and people who have hearing problems for other reasons (ototoxicity, autoimmune diseases, barotrauma and so on) should not hope for the development of this company? After all, the mechanism of damage is similar - death of external, or internal hair cells. In advance thanks for the answer.

 

I would assume it would work for the others as well. You just need to have some Lgr5+ progenitor (support) cells. They actually used drugs that kill hair cells prior to the trial to demonstrate that they could regrow them. The standard methods for pretrial experiments usually involves ototoxic drugs or exposing mice to loud sounds.

Now my concerns... Let's assume they get it to work for severe hearing loss and show a fair amount of restoration as they did in their paper. What we don't know is how well the treatment will work for people with mild hearing loss. I believe this market is even larger than those with profound hearing loss. For example, could you grow too many hair cells that cause some hypersensitivity or cause them to interfere with each other? My understanding is the cochlea has a very nice uniform matrix of hair cells and this forms this way by notch signaling between adjacent cells to prevent over crowding. It appears Frequency's small molecules temporarily defeat this and this the reason for my concern. Don't get me wrong. I'm extremely excited about this and their product makes far more sense than any of the others that are in trials. I keep praying this company will be the one that comes through.

 

I also pray this will work, I have the impression that yes it's possible, just let's hope soon enough (not ten years please ) so we can actually take advantage of it. When do they plan to do human trials ?

 

Around 12 to 18 month!

 

They are recruiting for Phase I trials now. Generally these are just a toxicity study. It is scheduled to complete in May 2018. The issue will be getting patients since the selection criteria is so stringent. Phase II will get more interesting, but that is probably a couple years out from now. The CEO spoke in a interview gave some coarse timelines that seemed pretty fast for clinical trials, I hope he is right.

https://clinicaltrials.gov/ct2/show/NCT03300687?term=FX-322&rank=1

 

Profound hearing loss will not be treated by frequency therapeutics because at that level the supporting cells and whole epithelium is gone. There's not much left to regenerate.

I don't think the concern is that they will grow too many haircells. Every new haircells you'd grow is based off existing supporting cells. But you're right that the uniform matrix and organization of haircells coming in is a concern. They've regrown haircells in China (don't forget this type of research is going on worldwide), but the organization of new haircells was mishapened and disorganized.

 

Do you have a link to the published paper where this happened?

 

That sounds scary. Using your supporting cells to regrow hair cells. How do they even know that these supporting cells dont have some massively important function in hearing that we don't understand yet?

 

That would be my fear is that the hair cells would be defective and perhaps make hearing sound more distorted or cause worse T

 

Frequency's technology involves making support cells divide and then signaling them to become hair cells. In theory you won't have any less support cells than before treatment. Genvec's gene therapy does not cause them to divide first and makes them convert. This is why I think frequency has a better approach.

 

I've talked directly with Will McClean on Reddit.

 

@parsky thank you very much for explaining that. It makes me feel a whole lot better!

 

Thanks for the answers grate_biff and parsky! I hope a couple of years isn't too far away, but then I see other companies are trying to do the same so maybe the concurrence is actually a good thing to get results sooner.

 

Sounds interesting. Do you have any links to papers describing these Chinese experiments?

 

On the "Frequency" site there is no information about aminoglycosides, or have I looked badly? In studies on mice, they use noise or antibiotics-aminoglycosides to artificially damage the ear to mice? And then they get to restore it ?! I also wrote a letter to the company. "Decibel terapeutics" (link- https://decibeltx.com) They also responded that they are working on a wide range of hearing loss. But while data on the timing and other things are confidential. What do you think about the prospects of this company? They also called to subscribe to their twitter - https://mobile.twitter.com/DecibelTx?lang=en

 

Decibel is a very promising company, but as you mentioned they are not going to elaborate on what they are doing. These companies are now competing with each other to come up with hearing loss cures and there is big money to be made. On a side note, it has been very quiet on the research front which could be a good or bad thing. I created a Decibel thread since none exists at this point so we can talk about them there and follow their accomplishments. Right now it seems like frequency has a plan moving forward and if succesful could be the first to come out with something that works.

The frequency trial is just as I had speculated. They will experiment on people that are severe to profound about to get cochlear implants. I'm still not sure how many healthy people will volunteer for the first trial since there is no hope of regaining any hearing. I know everyone was hoping that they would pick mild/moderate people with hearing loss and hopefully we will see this in the phase 2 trials.

I just wish they would hurry up since every day that passes people go from moderate to severe to profound and it seems like this won't work once a person's hearing gets that bad.

 

I think they just get people with profound hearing loss to see if it's safe? There's nothing more to loose and they can get a CI. Correct me if i'm wrong.

 

They are trialing these people because they were scheduled for an CI. They call it a safety trial, but its more to measure the concentration of their compound within certain time-intervals.

 

Okay Thanks. Really looking forward to the results.

 

I am not intellectual enough to fully understand this research, but I must say I am so exited that apparently so many companies are working on a cure/hair cell regeneration/different therapies.....is it really highly possible that we will have better treatment or some form of cure in the next 10 years?? I really really hope so.....

 

If the capital invested continues to grow the chances of getting a cure within the next decade also increases.
There's a ton of other research not directly related to tinnitus that also contributes for the likelihood of a cure, areas of research such as biophysics, neuropharmacology, molecular biology, and many more that will either give us insight into how these biological structures work more precisely, develop better instruments and/or give us new therapies.

 

Frequency Nabs $32M, Will Push Hearing-Loss Drugs To Human Studies
https://www.xconomy.com/boston/2017...ill-push-hearing-loss-drugs-to-human-studies/

The article says that, first of all, the frequency terapeutics is focused on noise-induced hearing impairment. I am also interested in ototoxicity. Are the mechanisms of damage so different that different methods of treatment are needed ?!

 

This article had me a bit concerned. "Edge cautions that the cocktail used in this study is likely too complex for use in humans, but he thinks it will enable researchers to manipulate large numbers of cochlear cells to boost hair cell populations with a single molecule."

https://cen.acs.org/articles/95/i9/Small-molecule-cocktail-reverse-hearing.html

So I take that to mean that FX-322 is something different from what was done for publishing that paper. I do understand that publishing a paper can take years, so the technique and cocktail used in the study could be "old".