Frequency Therapeutics — Hearing Loss Regeneration

If FX-322 worked and helped, I wouldn't be afraid to repeat the procedure... that would be the least of my concerns.

I have also read about 5-10 dB being insignificant on an audiogram. I just hope it isn't the case.

But if it's a real threshold shift, it's a win... The difference between 30 dB and 20 dB of hearing loss is significant.

 

Ask this person why none of the untreated ears improved word scores (and remember the audiologists were blinded in the study) and why some of the treated ears doubled (in the same patient)?

My audiologist told me doubling word scores was "unheard of."

 

I have 40 dB hearing loss at 4000 Hz.

It's very sad that FX-322 only works above 8000 Hz.

 

If I'm correct we don't know that yet and they are testing lower frequencies. The problem is getting FX-322 deeper into the cochlea where those frequencies reside. Hopefully eventually there will be a better delivery method.

 

We have no idea of the range of the phase 2a dosing. Carl LeBel has proposed that repeat dosing may extend the range and that's why the dosing is set up the way it is for phase 2a.

 

The 4/13 figure was strictly amongst the no placebo group.

 

I wouldn't simply say that this is solely about helping tinnitus. The likely view from most people is that they will want it to help both hearing and also tinnitus.

Also the type of comment that you just made about audiologists is typical of what I have seen when hearing and also reading commentary about audiologists from both the wider public and from other audiologists (usually the better audiologists). The biggest thing to note when it comes to the audiology field is that although they say that they have treatment as the number one interest, you will often find that there seems to be a large number of them who have hidden motives at play. This includes things like only dealing with two brands of devices and/or having individual charges for each visit too.

The view I have is that there might be many audiologists (and others we have observed making critical and/or negative comments on FX-322) that unfortunately have a vested interest in FX-322 being unsuccessful. This is because it will significantly shrink their market if there can be treatment obtained from FX-322. Unfortunately audiology is often viewed as a very profit focused industry due to the high number of practices which seem to operate in this way now.

There has been material which states what you have noted about the 5-10 dB increase, however what you said about a real shift of that amount being a win is also accurate. I have also seen material which says that 10 dB is meaningful. At this stage I think that it is a bit of a conflicting discussion between various bodies and people too.

I think that the thing that we still need to see some results on is whether there have been improvements in the very high frequencies and what these improvements were (if there were any at all). Furthermore, we will also need to see what the improvements were when it came to multi dosing. I know at the moment nothing is solid or completely confirmed when it comes to the very high frequency gains, however I think that the evidence looks somewhat promising.

What we have seen thus far is that the treatment outcomes seem to be solid for the most part. I am pretty sure that if most people have had stable improvements 20 months after they had the treatment, this is a good sign that the benefit will last too.

The commentary about needing to get the treatment redone at some point is probably the most interesting point for two main reasons.

Firstly, I view the negative commentary about needing to have the treatment redone as actually being a smokescreen. Something tells me that those who are actually making these types of comments are those who don't want to see this treatment have success.

I don't think that there has been evidence provided by anyone holding negative opinions about redosing which demonstrates why this is a negative outcome of FX-322 or why this shows that it is a poor treatment. I am pretty sure that there are already a number of medicines you have to retake at some point because the benefit that they provided will either eventually be diminished or it will only provide the benefit for a particular time frame.

Hell there have happened to be a number of vaccines I have had (like the Hepatitis C vaccine) which had to be redone because the first course was ineffective or didn't provide a long enough or big enough response. The second time that I took them ended up giving me the required response. I am pretty certain that my general practitioner stated that this is completely normal and that sometimes people need a bigger dose or redose of something for a number of reasons. Thus they said that this is not cause for concern at all, especially when a treatment or medicine is safe.

Secondly, I think that nobody would be complaining if they had to go get the treatment again if it was discovered that they needed a redosing to regain the lost benefit. Having said that, the information suggests that the way that this treatment works it is supposed to be lasting. I think that the results we have seen thus far tend to support that assessment.

Thus at this current time, I feel that there is no evidence to say that redosing is bad or is any cause for concern. Thus I cannot see what the issue with needing to redose would be, especially when this is not uncommon with medicines and also that there are seemingly no safety issues with FX-322. Therefore I think that there is no merit to this claim and that this is a case of people trying to make something look worse than what it actually is.

 

I think that this is fair, however having a look at ATOH and comparing it to FX-322 I think that both the techniques for the treatment and also the lab outcomes are different. Definitely know that the lab outcomes in FX-322 have been replicated elsewhere from what we have seen. The two dudes who originally found that the treatment being used at Frequency Therapeutics worked also had their results replicated by the guys at Frequency Therapeutics.

The dataset interpretations are also a point of contention, probably just like the discussions and debates on any scientific theory. The prominent problem with dataset reporting is that there are some set standards and also strict requirements when it comes to its reporting. I think that this has been evidenced in Frequency Therapeutics reporting from the Phase 1/2 trial. Frequency Therapeutics has clearly demonstrated that they have followed the data reporting rules that they are required to follow down to a tee. This is because Frequency Therapeutics knows that they have no choice and have been very focused on complying with all their FDA/reporting requirements.

Yet from a practical/real world perspective, many people would disagree with the fact that word score improvements of 71% is not considered statistically significant and would think this is a meaningful, beneficial and positive improvement. Thus I think that there are obviously times where you need to take the dataset outcomes with a grain of salt.

The funding issue is probably the most interesting point of discussion. I think that we are seeing that there are a number of universities and university based people being critical of these private companies and their research work because it is detracting from their influence within the sector and people are no longer viewing their outputs as the best any longer either.

For whatever reason, a lot of academics and universities actually think that academics and universities are the seminal and also ultimate bodies for undertaking research. The fact that a private firm or people working with a private firm can conduct research in an area and also get funding from bodies is an affront to them. Academics and also universities simply cannot comprehend being deemed to not have the best research work and/or proposals out of a number of candidates seeking to obtain funding grants. This is even more true when the candidate(s) which beat them come from the private sector.

The Rivolta situation you raised is an interesting and also good example of this as it demonstrated the work Rivolta is doing has a good case. Stanford seemingly didn't like this because this work of Rivolta took away possible funding which Stanford wanted for their own hearing related work and/or research.

This tells me that the work of the guy who has now started Rinri was simply superior and also that Stanford might have simply thought that they should have got the money because research is what they do.

It seems we are slowly seeing evidence which supports the claim that the university research is no longer necessarily as beneficial or as good as what we can see from the private sector.

Therefore when it comes to supposed experts making comments about another's research and/or work, I think it is not as important to look at the individual or organisation making a claim but rather we should be looking at whether the comment is being made cause the individual or organisation has got a vested interest that might be influenced by the other body's work.

I think that cases like the Rivolta one and also the FX-322 article have strongly shown us that this position is reasonable to take. At this time in both these cases, we have seen that the experts commenting will all have adverse outcomes on their own works due to the works of Rivolta and also Frequency Therapeutics. Thus in these cases you need to take what they have commented on with caution.

 

That isn't really how it works, though. Really the public and private sectors benefit each other and aren't in competition.

Public Universities: all initial research.

Private small cap biotech: takes a drug once it is in the pre-clinical stage and gets it to market.

Langer and Karp started the research on which Frequency Therapeutics is based in a university setting, just like all the other biotech startups.

Things might be different with the majors because they have a whole research and develop arm but small cap biotechs don't start with an "idea" and research it to market, that happens in the universities first.

It's possible that individuals have a conflict of interest but university research is not threatened by biotech start ups and vice versa. Literally the opposite.

 

I agree that your point has got merit to it, however I respectfully disagree that universities/university aligned research groups don't see private firms as a threat to their research.

In Australia there have been multiple instances of where a university or university aligned group has lost out on funding to a private individual who will be given funding to start a private firm to research a new area or try to come up with a novel and also breakthrough concept. The private individual obviously has work experience within the relevant field, however they actually come from outside the university sector.

The universities constantly complain that their purpose is being overlooked by allowing a private person to start the research work in this area and not affording them the opportunity to do this. The universities have also constantly raised that they should have been given the opportunity because research is the core of their operation.

Therefore while I agree that the universities are responsible for a large amount of the breakthrough and novel research into specific areas, there are also many cases where they are not.

 

Well... Frequency Therapeutics and your wonderful FX-322 would not be here today were it not for university research that laid the foundation of it all (Langer and Karp).

Same for nearly every single biotech out there currently working on regenerative medicine.

 

As I said in response to FGG, I don't disagree that the majority of new research comes out of universities. However what I am seeing more and more (and particularly in Australia) is that there are more and more individuals and groups outside the university sector who can obtain the support needed such as government funding to investigate and also complete novel research.

Furthermore we also have other private/non university affiliated research firms who run research work in exactly the same manner that all universities do. The universities have and can lose out on funding to these organisations too. The reason that we know this happens is because the universities express their displeasure at the decision.

I might be wrong and I apologise if I am, however I don't see why universities would be criticising the decisions of governments to award money to other firms if they didn't view them as a threat in some way. There is obviously a reason for their displeasure at not getting funding and I would say that this is a probable reason.

 

I'm not familiar with Australian biotech companies or the system there but in the US it's a lot more synergistic for drug development anyway.

Which biotech companies were competing with universities?

 

I don't remember specific names sorry. Usually the name of the company is never specifically mentioned because it usually isn't in existence at the time of the discussion.

 

It's extremely important to understand a lot of people don't want us to have a one-time use drug that cures your hearing. These people aren't thinking about our hearing, they are thinking about money. Keep this in mind when reading press release comments, articles, etc. Even other drug makers want to see certain drugs fail. Billions of dollars are at stake. Also. traders will comment in such a way to influence stock prices to their advantage. They don't care about what the drug even does, all they care about is 'buy low, sell high', 'pumping and dumping', etc... Snakes in the grass!

That said, there is still a chance this drug will not work at all for us. So it's important to not get your hopes up too high and to protect your ears in the meantime while we wait to find out. I do believe that even if this drug does fail at least it is a step in the right direction.

I would like to see the universities more involved with helping private companies getting their drugs pushed through the FDA process. The FDA is perfectly capable of offloading its review process to a university. They won't do this as long as they remain a spoon-fed entity of overrated nonsense.

10+ years to get a new drug approved by the FDA just seems so wrong to me. Then recently with the coronavirus vaccines getting rushed through the process in record time it really makes me question exactly what the FDA does. If the FDA botches the coronavirus vaccine trials we could see their FDA process gummed up even more.

 

The fact that they "weren't companies yet" was sort of my point.

No single government grant to a biotech (I'm not even sure in the US they give these too often except for military contracts anyway) without a remotely near term product could make up financially for what is often decades of research leading up to that point (immediately pre-clinical studies).

There wouldn't even be a small cap biotech company founded before there was a potential product to sell because people tend not to invest in companies without a definite plan or remotely near term product.

If anything, companies like Frequency Therapeutics and Otonomy being further along than Novartis (which does have a research and development arm since it is a major pharmaceutical company), shows how much the University research is needed as an adjunct to biotech start ups.

It the US, public universities and private biotech are *both* vital for research.

 

Now I am understanding your point better, sorry.

Australia is somewhat different in the way things are done to the US and as a result I think I am probably not suited to comment on how US funding works when I am not familiar with it. I definitely don't disagree that there is an essential need for both the university/public sector research firms and the pivate sector to work simultaneously with one another. Absolutely the only way we will ever get best results.

 

He said it might extend the range or it might make the effect stronger in the current range or it might provide an effect in more people. They don't know, so that's why they're doing it.

 

So, Frequency Therapeutics will be presenting later today at the Cantor Fitzgerald conference - there should be a webcast available according to the press release.

 

David Lucchino was featured on Bloomberg Radio recently discussing FX-322:

https://www.bloomberg.com/news/audio/2020-09-14/baystate-business-governor-patrick-radio

 

Woo! Been a while since I last posted here! Looks like we've got a few new regulars, and we're back on the old anxiety carousel!

I'll drop this here, and then I'll see you all in a week:

https://investors.frequencytx.com/static-files/47014168-736e-4a25-9435-b1a8bf19599e

My thoughts from the recent PR sweep:

1. The drug works, it just doesn't go deep enough. The long-term "durability" study reinforces that notion.

2. Word scores improved after 90 days from the Phase 1/2, then declined slightly for some, while others fell back to baseline. It's highly likely that the part of the patient's cochleas that didn't see improvement from FX-322 still continued to age; explaining the reduction in word score. In other words, the word score likely fell because everything under 8 kHz continued to wear. Which brings me to my next point:

3. The fact that most patients retained their hearing at 8 kHz up to 2 years later from the original dosing is ACTUALLY HUGE. That could be interpreted as those new cells above 8 kHz are hanging on, like new, just as intended from the PCA approach.

4. I would believe researchers over audiologists. Audiologists see an inevitable paradigm shift in their industry; so will say anything to discredit a direct challenge. Researchers responding to FX-322's progress are looking at the data; they seem to continue to give a balanced review (it's compelling data, but we need more). Do a little research about LASIK when it first started to pick up steam in the 90s (in the US)... there was some negative PR from glasses manufacturers and eye care coalitions.

5. Frequency Therapeutics seems to be getting a little more loose about revealing the "anecdotes about patients tinnitus improving." This shows confidence. I would not be surprised if in the long-term durability study, patients were interviewed re: how their tinnitus was doing.

6. Frequency Therapeutics is planning on testing FX-322 for Severe Hearing Loss and Age-Related Hearing Loss. Look for updates on those two studies between now and the Phase 2A results being released. They could easily do them with their on-going university relationship in Texas. I would GUESS that the measured outcomes will look a lot like the Phase 2A. Could be a winter 2021 surprise!

 

I like your style .

 

Thanks for the reassurance. I was just going to say that people seem a lot more skeptical ever since Frequency Therapeutics put out that update. Maybe it's natural for people to hyper-analyze any little update Frequency Therapeutics puts out since they're so few and far in between.

 

Also something encouraging is that in the Bloomberg broadcast Carl LeBel mentioned a 30-year-old workout fanatic contacting him because of damage sustained to the ears due to loud headphone use, it's likely this dude had and mentioned tinnitus to Carl. He implied that it would be helpful for people like him as well.

 

The more demand/customers/potential profit there is, the quicker a successful drug will reach the market. The fact is more and more people are abusing their ears with headphones. I wouldn't wish tinnitus/hyperacusis on anyone but in the next few years it's going to be a very common affliction.

 

I'm pretty sure sustained headphone usage over the years is the prime culprit in my hearing problems. I haven't listened to the Bloomberg piece because I want to avoid a spike but this is encouraging!

 

Taking doctor's views as fact is so 20th century

 

Can somebody explain to me why FX-322 would work for some but not for others (outside of hair cell death, same level of expertise of doctor injecting it etc)?

Or should it work for everyone?

 

I remember reading somewhere, though not sure if true, that 20% if people have bad round window permeability. Maybe someone more knowledgeable can opine.

 

1. I absolutely agree about FX-322 working effectively but currently not going deep enough in the ear. I think that there is a lot more confidence with the stability and durability of the treatment results and benefits now that we have seen these outcomes. I think this is why the drug delivery methodology is going to be the major focus from Frequency Therapeutics in the near future. Finding ways to improve the drug delivery is seemingly the missing link and this will improve not only the benefit provided by FX-322 but also increase the number of people who can be assisted by taking FX-322.

At this point in time, I can clearly see that either the companies making these ear medicines like Frequency Therapeutics or drug delivery companies will initiate work to improve the dosing. It is obviously in the interests of the medicine development companies like Frequency Therapeutics to improve the effectiveness of delivery as this will mean it is possible to treat a wider group. However if a drug delivery company or companies can come out with improved techniques then they can provide this to all companies who are manufacturing ear medicines. This is a highly positive situation, as drug delivery companies now have a potentially highly profitable market to work with. Thus there will be huge interest in this project from the drug delivery sector and drug delivery companies and I am sure that we will see significant work take place. Pretty sure we have already seen the foundations laid for this type of work with the investigations and research into dosing via cochlear pumping techniques and that there will be more of this type of research continuing.

2. Your position that word scores fell due to a worsening at some lower frequencies is probably a fair summation. However I would also wonder whether there was some other factor at play. I would probably wait to see some further results to confirm that worsening at the lower frequencies was the cause. This is because while this is a likely cause, there are still some unknowns around the actual benefits of FX-322 and also there has only been limited testing done to date.

3. The fact that the benefits of the FX-322 have been maintained 20 months after administering it tells me that this further demonstrates that the FX-322's performance appears to be legitimate and that the benefit is real. Furthermore it shows that this progenitor cell activation process is an effective and legitimate technique. I agree with you that this is huge and also a major breakthrough. This shows me that the process does work and makes me feel very confident.

4. The LASIK comparison is highly relevant when it comes to looking at FX-322 and the views that some bodies and some individuals have towards it. While some entities have been balanced in their commentary about FX-322 and its performance and capabilities, there have been other entities who have been reasonably keen to be negative/critical of FX-322 too.

Based off of the information I have found out about when LASIK started in Australia, it seems that some in the eye care industry were very focused and keen on using whatever information they could to paint LASIK in a negative light. This didn't just include plausible and valid negative information (such as the cost of the treatment) but also groups were widely interested in using positive outcomes from early treatment using LASIK to try and show why it was not necessarily a good choice of treatment. We have also seen these tactics used by those who are against and are critical of FX-322.

I think that this is going to be a likely tactic used by groups like hearing aid manufacturers. The issue in Australia was that glasses used to be expensive and cost $400 a pair in mid 90s and actually now cost $99 for a reasonably good pair at the big brand/chain glasses stores. Optometrists were never going to admit this, though it is blatantly obvious that their criticism and concerns about LASIK were financially driven.

I can see this also playing out with hearing aid manufacturers, as they will have their business potentially reduced if treatment like FX-322 means that fewer people are using the hearing aids and/or people are only needing to utilise the basic devices.

In the end however, LASIK won out and became a highly viable option/alternative to glasses once it could be demonstrated the effectiveness and safety of the LASIK procedure was to a high standard.

I believe that the companies undertaking FX-322 and related treatments will simply have to go hard on the messaging and the information campaigning. My memories of watching TV as a child were that there were LASIK ads bombarding the TV to inform people of this option. The end result was that they helped to build up the knowledge of the procedure and thus candidates were willing to have the procedure. This meant others could now have first hand accounts of the procedure (such as what I was like and how it went) from others. This in turn then meant more people took up LASIK because if they previously had concerns these were being alleviated by the evidence from the procedure outcomes.

Thus I can see all regenerative treatments needing to follow the same path because not only are they going to need to educate people on the potential benefits of this treatment but this is also the most effective way to negate the resistance from the status quo.

5. I know that Frequency Therapeutics need to remain rather guarded and cautious when it comes to what information they release so they don't infringe the FDA/stock market rules, however I actually think that the fact that they have released some small unofficial hints about the benefits of the treatment and what is going on is promising progress and also going to make people feel more confident. I am pretty positive that the cryptic clues that Frequency Therapeutics has released about FX-322 give us a good insight in to what FX-322 can potentially do and also what Frequency Therapeutics will be doing in the future.

6. Although we don't know what is happening internally, I must say that that the decision to expand the scope of the operations to look at some other treatment groups for example definitely suggests some positive progress is being made and also that Frequency Therapeutics is robust. Right now I think that this is a good sign of progress.