Frequency Therapeutics — Hearing Loss Regeneration

[Princebeyel]

No, I wrote on March 4th:

At the moment we are at minus 17 percent.

I still have doubts about a successful story. In my most optimistic opinion, I guess the clinical trial will show that a smaller part of the participants show some improvements and an even more smaller part will report maybe minimum tinnitus improvements.

The bad thing is, I got the nickname "Hiob" (I don't know how many are bible-proof here) by my best friends already in school, as I predicted several little bad things (not terrible things).

Hey Mr. Toby, can you tell us when they are going to release these Phase 2 90-Day results with that crystal ball of yours?

 

[Toby1972]

Hey Mr. Toby, can you tell us when they are going to release these Phase 2 90-Day results with that crystal ball of yours?

Wait... hmmn. Ommm. It will be in the future.

 

[Aaron91]

No, I wrote on March 4th:

At the moment we are at minus 17 percent.

I still have doubts about a successful story. In my most optimistic opinion, I guess the clinical trial will show that a smaller part of the participants show some improvements and an even more smaller part will report maybe minimum tinnitus improvements.

The bad thing is, I got the nickname "Hiob" (I don't know how many are bible-proof here) by my best friends already in school, as I predicted several little bad things (not terrible things).

Sounds like someone is backtracking:

1) You said last week that they faked their Phase 1 results, that you were "certain" they would post negative Phase 2 results, that the stock price was down because of "insider selling" (even though insiders must file their sales with the SEC months in advance lmao) and that you had sold at the maximum price FREQ will ever reach.

2) Now you're saying "you have doubts" as opposed to be being certain, and that some people may actually show improvements!

3) Next week, when they post good data, you'll be saying you always thought it was possible it would happen and that you're not surprised.

You are literally letting market prices affect your opinion on the potential success of the drug, with no regards to other forces at play, which tells me you actually understand very little about how the market works. In fact, your post history would suggest you know just as much about the drug as you do about the stock market: zero.

 

[Aaron91]

So for anyone who still has doubts, I present to you the event schedule for 17 March (attached).

The two people presenting are Will McLean, the very man who invented FX-322 and who knows the drug and science better than anyone (I posted a video of him a couple of pages ago), and Kevin Franck, who is their most recent appointment responsible for marketing and product planning. If this doesn't scream to you that Frequency have a product they know will get to market I don't know what does. Also, take note of the title of their presentation:

"Advances in Hair Cell Regeneration for Acquired Sensorineural Hearing Loss"

 

[Zugzug]

Me when @FGG, @Diesel, and @HootOwl drop well-reasoned and encouraging knowledge bombs on us:

View attachment 43838

If you're Jesse, I'm so sorry. You are in for a rough ride. The people you are praising may be manipulating you.

 

[leledany]

The failure of FX-322 could be a possibility... If it is a success, there should be rumors by now, shouldn't there?

 

[Greg Sacramento]

@Toby1972, it was almost a given with charting with red appearing at $48 that stock price would consulate. Hedge funds had let the price rise about 6 more points because they saw retail optimism. Some retail also sold in the 50's.

I like what Frequency Therapeutics is doing for us, more than what yearly profits may be. Stock price may not reflect how Frequency Therapeutics will change the lives of many here for the better. One of few concerns is getting all healthcare needed properly trained. We don't know much about pricing at this time either.

Several good technical forecasters see a NASDAQ stock correction. I'm not quite so sure, need to see development of a few indicators first. As long as the FED in the USA are giving us money, consumer goods should do well and with the virus getting controlled, more people will be out and about spending. I don't see inflation or interest rates as a concern.

 

[HootOwl]

Wait... hmmn. Ommm. It will be in the future.

I would also like to know when my beautiful and lonely 7 GME shares will finally land on Pluto, plz and thank you.

 

[HootOwl]

If you're Jesse, I'm so sorry. You are in for a rough ride. The people you are praising may be manipulating you.

@FGG is obviously the most sinister and Machiavellian of our rag-tag crew.

 

[Paulmanlike]

So for anyone who still has doubts, I present to you the event schedule for 17 March (attached).

The two people presenting are Will McLean, the very man who invented FX-322 and who knows the drug and science better than anyone (I posted a video of him a couple of pages ago), and Kevin Franck, who is their most recent appointment responsible for marketing and product planning. If this doesn't scream to you that Frequency have a product they know will get to market I don't know what does. Also, take note of the title of their presentation:

"Advances in Hair Cell Regeneration for Acquired Sensorineural Hearing Loss"

Was it Will McLean who invented FX-322? I always thought it was Langer and Karp?

Either way, he's definitely hiding the cure for hearing loss and tinnitus in that beard!

 

[FGG]

@Toby1972, it was almost a given with charting with red appearing at $48 that stock price would consulate. Hedge funds had let the price rise about 6 more points because they saw retail optimism. Some retail also sold in the 50's.

I like what Frequency Therapeutics is doing for us, more than what yearly profits may be. Stock price may not reflect how Frequency Therapeutics will change the lives of many here for the better. One of few concerns is getting all healthcare needed properly trained. We don't know much about pricing at this time either.

Several good technical forecasters see a NASDAQ stock correction. I'm not quite so sure, need to see development of a few indicators first. As long as the FED in the USA are giving us money, consumer goods should do well and with the virus getting controlled, more people will be out and about spending. I don't see inflation or interest rates as a concern.

I think another possible factor is the fact that Biden hasn't named a new FDA head either and investors hate the uncertainty of knowing how conservative or not the new head will be. I think some are waiting to jump back into the sector on that news.

 

[RB2014]

@Toby1972, it was almost a given with charting with red appearing at $48 that stock price would consulate. Hedge funds had let the price rise about 6 more points because they saw retail optimism. Some retail also sold in the 50's.

I like what Frequency Therapeutics is doing for us, more than what yearly profits may be. Stock price may not reflect how Frequency Therapeutics will change the lives of many here for the better. One of few concerns is getting all healthcare needed properly trained. We don't know much about pricing at this time either.

Several good technical forecasters see a NASDAQ stock correction. I'm not quite so sure, need to see development of a few indicators first. As long as the FED in the USA are giving us money, consumer goods should do well and with the virus getting controlled, more people will be out and about spending. I don't see inflation or interest rates as a concern.

The NASDAQ did correct and then we were handed another stimulus. I have a feeling this could be the last stimulus and if so that NASDAQ correction might happen after that. Agreed, that as long as the US is giving everyone free money... nothing bad is going to happen, but that can't last forever. We are in so much debt...

 

[Toby1972]

Sounds like someone is backtracking:

1) You said last week that they faked their Phase 1 results, that you were "certain" they would post negative Phase 2 results, that the stock price was down because of "insider selling" (even though insiders must file their sales with the SEC months in advance lmao) and that you had sold at the maximum price FREQ will ever reach.

Aaron, I was certainly not "certain" and I was not claiming that there was any insider selling, I was just asking questions and I've thrown hypotheses in the room to discuss:

If I wanted to target billions of fraud myself and would like to fake it, it wouldn't be so difficult to find 4 people who pretend they don't understand anything in the first test and then recognize more words a few weeks later.

As a stock market expert, it seems like this to me: This is an insider move.

So I don't want us to have an ongoing meaningless dialogue? That wastes time, I don't want to waste their precious time.

And believe me, my best friends know that I am one of the most positive people there can be and that I am also generous and compassionate and take great care of the well-being of others.

Without my positive thinking, I would not have survived my Agranulocytosis with Pneumonia, Sepsis and Pulmonary Lobe removal in 2019.

And in 2020, after 3 days without sleep due to tinnitus, I had already googled how I could comfortably get a "final" injection in the not far away Netherlands.

I hope for you at least as much as for me that we will find healing and pray (to my higher being, whatever it looks like, I know that I had help in 2019) for you too.

If Phase 2a is successful, and we will be cured of tinnitus ( and/or your hyperacusis) at some point, I will invite you to Oktoberfest (I live only 30 km away) and get you free to drink beer - a liter of beer is not cheap, believe me... But I can afford it with my expert knowledge for the stock market...

 

[Aaron91]

Was it Will McLean who invented FX-322? I always thought it was Langer and Karp?

Either way, he's definitely hiding the cure for hearing loss and tinnitus in that beard!

The story is that Jeff Karp's and Robert Langer's labs jointly developed it, but if you pull back the curtain you will realise that a lot of the leg work was done by two people in particular: Will McLean, a co-founder, and another man called Xiaolei Yin, who currently sits on the PCA advisory board for Frequency Therapeutics. I don't think many people know actually who did what, so I'll do my best to explain.

Will had been doing some general research into hearing regeneration and he was trying to trace the lineage of auditory cells in mice during their development i.e. which specific cells became hair cells, which cells became neurons etc. Without going into detail, he managed to develop these biological markers where you could literally track different types of cells through their lineage by their colour (this is actually a lot more difficult than it sounds). It was in this work that he was able to identify that it was the LGR5 progenitor cells specifically that turned into hair cells and not any other cells. In other words, he found the smoking gun with regards to which cell was responsible for making us hear. The problem was, as we all now know, that these cells stop regenerating after birth. It was known humans could not regenerate their hearing, but it wasn't known which cells were responsible for generating hearing cells in the first place. So now that Will McLean knew which cells to target, he was looking for a way to see if he could "switch" them back "on". Step in Xaiolei Yin.

Xaiolei had been doing some work on the intestine in the same lab at the same time as Will. The intestine was already known at this point to be one of the few active regenerative tissues in the body. The lining of the intestine regenerates every day 5 to 7 days. Now, I'm unsure as to whether Xaiolei discovered this or whether this was known previously, but the fact was that LGR5 progenitor cells in the intestine had been identified at some point as also being the "smoking gun" for regenerating the intestine cells. The difference was that these cells were accompanied by something called paneth cells, which provided the cellular signalling for the LGR5 cells to keep regenerating and producing intestine cells. Xaiolei was able to show that through a combination of turning Wnt and notch on/off (the signal pathways) using small molecules, he was able to emulate the effect of the paneth cells and produce colonies of all the different types of intestine cells one needed for the intestine.

This is where Xaiolei's work collided with Will McLean's. LGR5 cells in the cochlea, having been identified by Will as the cells responsible for generating hair cells, became a convenient testing ground for Xaiolei's work. The rest is history: they applied the small molecule approach to the LGR5 cells in mice cochlea and ex-vivo human cochlea which lacked the signal pathways required for regeneration (due to no equivalent of paneth cells) and were able to fully regenerate hair cells throughout the cochlea. They also showed that the process was self-limiting, in that once enough cells had been regenerated, the process stopped.

All this work was done in the labs of Karp and Langer, but these guys really did knock it out of the park.

 

[HootOwl]

If Phase 2a is successful, and we will be cured of tinnitus ( and/or your hyperacusis) at some point

I believe this quote here is also kind of concerning, and part of the reason why others are giving you a hard time and claiming you have a fundamental misunderstanding of both the drug itself, and the stock market as a whole.

FX-322 is not going to be a cure for "capital T" tinnitus. It is one tool in a (hopefully) ever-expanding tool-kit that will include various other forms of regenerative and anti-inflammatory medicine.

Surely if you read the thread in its entirety you would know, and understand this? It's a little sus.

 

[Aaron91]

Aaron, I was certainly not "certain" and I was not claiming that there was any insider selling

That is exactly what you said though.

"I am becoming more and more certain that the FX-322 will not cure tinnitus"

As a stock market expert, it seems like this to me: This is an insider move. You recognize that Phase 2 is ineffective, and so that you can still find inexperienced buyers, you send out a positive message so that you can still sell profitably.

In any case, I would like to take you up on your kind offer below:

If Phase 2a is successful, and we will be cured of tinnitus ( and/or your hyperacusis) at some point, I will invite you to Oktoberfest (I live only 30 km away) and get you free to drink beer - a liter of beer is not cheap, believe me... But I can afford it with my expert knowledge for the stock market...

I would like one beer please for every member on this forum who ends up being treated and/or cured of their tinnitus/hearing loss/hyperacusis by FX-322. I am happy to receive the supply in truck loads of barrels

 

[Diesel]

he was able to emulate the effect of the paneth cells and produce colonies of all the different types of intestine cells one needed for the intestine.

So, is it the paneth cells producing the molecular combination, or a similar molecular combination to VPA + CHIR in FX-322?

 

[Tezcatlipoca]

The story is that Jeff Karp's and Robert Langer's labs jointly developed it, but if you pull back the curtain you will realise that a lot of the leg work was done by two people in particular: Will McLean, a co-founder, and another man called Xiaolei Yin, who currently sits on the PCA advisory board for Frequency Therapeutics. I don't think many people know actually who did what, so I'll do my best to explain.

Will had been doing some general research into hearing regeneration and he was trying to trace the lineage of auditory cells in mice during their development i.e. which specific cells became hair cells, which cells became neurons etc. Without going into detail, he managed to develop these biological markers where you could literally track different types of cells through their lineage by their colour (this is actually a lot more difficult than it sounds). It was in this work that he was able to identify that it was the LGR5 progenitor cells specifically that turned into hair cells and not any other cells. In other words, he found the smoking gun with regards to which cell was responsible for making us hear. The problem was, as we all now know, that these cells stop regenerating after birth. It was known humans could not regenerate their hearing, but it wasn't known which cells were responsible for generating hearing cells in the first place. So now that Will McLean knew which cells to target, he was looking for a way to see if he could "switch" them back "on". Step in Xaiolei Yin.

Xaiolei had been doing some work on the intestine in the same lab at the same time as Will. The intestine was already known at this point to be one of the few active regenerative tissues in the body. The lining of the intestine regenerates every day 5 to 7 days. Now, I'm unsure as to whether Xaiolei discovered this or whether this was known previously, but the fact was that LGR5 progenitor cells in the intestine had been identified at some point as also being the "smoking gun" for regenerating the intestine cells. The difference was that these cells were accompanied by something called paneth cells, which provided the cellular signalling for the LGR5 cells to keep regenerating and producing intestine cells. Xaiolei was able to show that through a combination of turning Wnt and notch on/off (the signal pathways) using small molecules, he was able to emulate the effect of the paneth cells and produce colonies of all the different types of intestine cells one needed for the intestine.

This is where Xaiolei's work collided with Will McLean's. LGR5 cells in the cochlea, having been identified by Will as the cells responsible for generating hair cells, became a convenient testing ground for Xaiolei's work. The rest is history: they applied the small molecule approach to the LGR5 cells in mice cochlea and ex-vivo human cochlea which lacked the signal pathways required for regeneration (due to no equivalent of paneth cells) and were able to fully regenerate hair cells throughout the cochlea. They also showed that the process was self-limiting, in that once enough cells had been regenerated, the process stopped.

All this work was done in the labs of Karp and Langer, but these guys really did knock it out of the park.

That story should be on the history books. That's amazing.

 

[Zugzug]

The story is that Jeff Karp's and Robert Langer's labs jointly developed it, but if you pull back the curtain you will realise that a lot of the leg work was done by two people in particular: Will McLean, a co-founder, and another man called Xiaolei Yin, who currently sits on the PCA advisory board for Frequency Therapeutics. I don't think many people know actually who did what, so I'll do my best to explain.

Will had been doing some general research into hearing regeneration and he was trying to trace the lineage of auditory cells in mice during their development i.e. which specific cells became hair cells, which cells became neurons etc. Without going into detail, he managed to develop these biological markers where you could literally track different types of cells through their lineage by their colour (this is actually a lot more difficult than it sounds). It was in this work that he was able to identify that it was the LGR5 progenitor cells specifically that turned into hair cells and not any other cells. In other words, he found the smoking gun with regards to which cell was responsible for making us hear. The problem was, as we all now know, that these cells stop regenerating after birth. It was known humans could not regenerate their hearing, but it wasn't known which cells were responsible for generating hearing cells in the first place. So now that Will McLean knew which cells to target, he was looking for a way to see if he could "switch" them back "on". Step in Xaiolei Yin.

Xaiolei had been doing some work on the intestine in the same lab at the same time as Will. The intestine was already known at this point to be one of the few active regenerative tissues in the body. The lining of the intestine regenerates every day 5 to 7 days. Now, I'm unsure as to whether Xaiolei discovered this or whether this was known previously, but the fact was that LGR5 progenitor cells in the intestine had been identified at some point as also being the "smoking gun" for regenerating the intestine cells. The difference was that these cells were accompanied by something called paneth cells, which provided the cellular signalling for the LGR5 cells to keep regenerating and producing intestine cells. Xaiolei was able to show that through a combination of turning Wnt and notch on/off (the signal pathways) using small molecules, he was able to emulate the effect of the paneth cells and produce colonies of all the different types of intestine cells one needed for the intestine.

This is where Xaiolei's work collided with Will McLean's. LGR5 cells in the cochlea, having been identified by Will as the cells responsible for generating hair cells, became a convenient testing ground for Xaiolei's work. The rest is history: they applied the small molecule approach to the LGR5 cells in mice cochlea and ex-vivo human cochlea which lacked the signal pathways required for regeneration (due to no equivalent of paneth cells) and were able to fully regenerate hair cells throughout the cochlea. They also showed that the process was self-limiting, in that once enough cells had been regenerated, the process stopped.

All this work was done in the labs of Karp and Langer, but these guys really did knock it out of the park.

You should write Wikipedia pages. This was highly informative.

 

[Born To Slay]

The failure of FX-322 could be a possibility... If it is a success, there should be rumors by now, shouldn't there?

With that logic, there'd be rumors of failure also.

 

[Paulmanlike]

@Aaron91, thanks for the info. I've learnt something new today and understood it all.

There was a member here a while ago, @Aaron123. Are you the same person? He was one of my favourite members of Tinnitus Talk and he disappeared. Very informed guy and straight to the point.

 

[Aaron91]

So, is it the paneth cells producing the molecular combination, or a similar molecular combination to VPA + CHIR in FX-322?

I think to answer this question I'm going to have to go away and read Xiaolei's work again and get back to you.

Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny

In any case, I'm not confident I'll have an answer for you lol.

It isn't entirely clear to me whether the two pathways are activated by molecules exclusively or whether they can be activated by some other cellular mechanism and this is where I really wish I had a background in this stuff. What I do understand is that what it ultimately comes down to is changes in gene expression, because that is the end point in terms of the final domino that falls in the pathway, if I'm not mistaken. Everything that happens in between is so complex I gave up trying to understand some time ago.

The concern of course with playing around with gene expression is that you risk cancer and if you look at some youtube videos on the wnt pathway, it says that cancer can happen when the pathway goes out of whack. This is what I find most incredible about their work, because as I said above, the process was self-limiting. If I remember correctly, the way Will McLean spoke about this in his lecture came off as almost as a surprise. I don't think they planned it, not that they wouldn't want it to be self-limiting, of course. So I think what we are seeing is truly a case of the system being fooled into thinking it's in the womb again, and so clearly the gene expression has been nailed. The fact they got there using VPA and CHIR or something equivalent seems to me to be a bit superfluous, but of course it wouldn't surprise me if that were the case given how perfectly they seem to have nailed it.

I know this wasn't asked but my own personal theory, which I briefly mentioned in the Pipeline Therapeutics thread, is that although VPA has an affect on the notch signalling pathway, I think it's plausible that it may have some other role in allowing CHIR to transcribe genes that it otherwise cannot on its own because of its ability to prevent deacetylation (I know some people will be wondering what the hell that even means and I will endeavour to write something up another time). @FGG has also pointed out that although VPA stimulates notch it inhibits part of the cascade. So all this says to me is that VPA fulfils a very, very specific role, suggesting then that it was purposefully chosen, but at the same time the way Will McLean spoke about the self-limiting behaviour would suggest that they may have also been shooting in the dark a little bit as well.

You should write Wikipedia pages. This was highly informative.

Ah, thanks @Zugzug, you're always too kind! Given my career got turned upside down from my condition I'm going to have to pivot into something else eventually lol.

@Aaron91, thanks for the info. I've learnt something new today and understood it all.

There was a member here a while ago, @Aaron123. Are you the same person? He was one of my favourite members of Tinnitus Talk and he disappeared. Very informed guy and straight to the point.

I'm not, but I hope there's space for two Aarons on here

 

[Christine2222]

15 more business days people... we're in the home stretch.

 

[Tezcatlipoca]

15 more business days people... we're in the home stretch.

Next Wednesday, tops.

 

[Lucifer]

This is how I'm going to feel when I get the FX-322 cure for tinnitus and hyperacusis.

 

[AtlasFainted]

I think another possible factor is the fact that Biden hasn't named a new FDA head either and investors hate the uncertainty of knowing how conservative or not the new head will be. I think some are waiting to jump back into the sector on that news.

Considering that it was Trump who opened up Compassionate Use, I doubt Biden's new FDA head will be willing to break down bloated FDA regulations.

It was also Trump's head of the FDA that said last year that regulation reform is needed. Of course haven't seen any action taken to backup that sentiment...

It seems like Biden more or less wants to do the opposite of what Trump did. So if Trump made access a little easier, I'd imagine Biden's pick will ultimately make it harder. The Executive Order that affected insulin is a good example of this.

I could be wrong though, and I hope I am!

 

[d'Wooluf]

David Lucchino has usually taken the big announcements upon himself. Don't count your chickens.

 

[FGG]

David Lucchino has usually taken the big announcements upon himself. Don't count your chickens.

What do you mean?

 

[Rb86]

What do you mean?

I think he means don't expect the announcement to come at the presentation on the 17th.

 

[FGG]

I think he means don't expect the announcement to come at the presentation on the 17th.

Ah. Yes. I expect Lucchino to make the announcement right before the presentation but not at the presentation. But just a guess.