Frequency Therapeutics — FX-345

The filing process is happening right now. Should be done sometime in H2:2022.

 

Just as long as they stick to the timetable. These delays prolong my depression. Just imagine if they actually start injecting people with this stuff in the fall. It's not that far away.

 

I have high hopes for this one. Both for hearing loss and hopefully (fingers crossed tinnitus).

Bob Langer is a living legend and the grads from 'Langer Labs tend to do very well.

Bit concerned about financing after 2023 but if the FX-345 IND results are great then I am sure Astellas will be forthcoming with a deal. Not sure if the deal for FX-322 extends to FX-345. Time will tell but this company (and hearing loss and tinnitus sufferers) need good news from the FX-345 and the 208 trial for FX-322.

If the company meets endpoints with the 208 Phase 2 trial, it could trigger milestone payments from Astellas.

There is no doubt that early 2023 is a make or break point for Frequency Therapeutics. I sincerely hope they make it.

 

It seems early 2023 is important to several of these companies. Otonomy has enough cash to get until the spring of '23, for example. These companies need to show consistent results, and soon. I'm pulling for all of them.

 

I think the same.

I hope the company survives in order to find a drug for us. It seems that their share price is at its lowest in their history.

 

It's common for public biotech to issue more shares and then sell those shares at a set price to raise capital.

More than half of all Frequency Therapeutics shares are presently owned by institutions, including notables Blackrock, Vanguard and JP Morgan.

These institutions would certainly purchase new shares if needed to raise corporate capital for Frequency Therapeutics.

 

That's a little creepy that all those own it. I mean, good for Frequency Therapeutics, those are the biggest dogs around. But I'm extremely concerned of Blackrock / JP Morgan owning anything that matters...

 

I agree. Manipulators of currency and futures.

Top Institutional Holders for FREQ

Holder Shares
Wasatch Advisors Inc 3,166,962
Blackrock Inc. 3,044,997
Federated Hermes, Inc. 2,801,066
Vanguard Group, Inc. (The) 1,457,220
JP Morgan Chase & Company 1,167,477
South Dakota Investment Council 716,726
Lombard Odier Asset Management (Switzerland) SA 707,071
State Street Corporation 598,590
Geode Capital Management, LLC 574,890
Jacobs Levy Equity Management, Inc. 317,837

Top Mutual Fund Holders for FREQ

Holder Shares
Wasatch Small Cap Growth Fund 1,145,884
Federated Hermes Kaufmann Small Cap Fund 1,000,000
Federated Hermes Kaufmann Fund 1,000,000
Wasatch Ultra Growth Fund 902,826
Vanguard Total Stock Market Index Fund 793,072
iShares Russell 2000 ETF 749,397
Vanguard Extended Market Index Fund 445,127
Wasatch Microcap Fund 351,606
iShares Russell 2000 Value ETF 325,597
JP Morgan Small Cap Value Fund 322,700

 

I personally think FREQ will get funding BUT it is dependent on FX-322 208 and in particular FX-345 results which are pivotal.

Those are an impressive list of varied institutional investors BUT they will want good results from trials in order to commit more capital. The market sentiment towards this company as an investment is very low. The share price doesn't lie (well apart from manipulation).

At the present market capitalisation FREQ would want 3 or 4 times the market cap in funding in order to cover existing costs and PHASE 3 FX-322 and FX-345 PHASE 2 for the two year duration of those trials.

Their funding requirements also depend on Astellas' royalty. Will Astellas' progress FX-322? I doubt it. I can't see the commercial appeal of FX-322 based on existing data BUT that is just my opinion.

FX-322's future lies in the hands of Astellas I feel. If they want a Phase 2B in Europe and Asia, the milestone payments will cover a FREQ sponsored PHASE 3 in the US.

Astellas would be better off buying FREQ outright in a takeover in my opinion. That is certainly a possibility.

Either way if FX-345 gets sub 4,000 Hz and shows strong efficacy from 4,000 Hz and above then this will be a blockbuster and funding concerns will be irrelevant.

It all hinges on FX-345 imho. It would be epic for us hearing loss sufferers if it succeeds.

 

Does anyone believe FX-345 will show improvements in pure tone audiometry?

 

I contacted Astellas in Prague and London. What I heard from them is that they don't plan any clinical trials with Frequency Therapeutics, but I only had two calls, not really sure if they were with relevant people.

It's a shame Astellas hasn't brought clinical trials to EU so far; like what is the point of buying the rights for FX-322 and not use them in EU or Asia? Like wtf, if they don't want to bring this drug to EU, why the heck don't they leave it for someone else.

 

This is the license and collaboration agreement between Frequency Therapeutics and Astellas. Noted are the extremely valuable MIT patents. Actual MIT patents are not discussed in this agreement, but their legal binding is as long as this licensing agreement. These patents are licensed with Frequency Therapeutics and Astellas has no authorization to use them separately. For this reason alone, Astellas will continue to fund Frequency Therapeutics. All the Institutional holders know this and this why they haven't lowered their share ownership.

https://www.sec.gov/Archives/edgar/data/0001703647/000119312519239976/d72917dex1012.htm

 

Patents are only valuable if the tech behind them works. FX-322 has not shown enough in clinical trials yet to be considered a marketable drug (the share price on Phase 2 tells you that).

FX-345 is a complete unknown with a new compound and no results yet in humans.

Astellas have no reason to continue to fund Frequency Therapeutics if the tech does not work. PCA is not a sure bet. If it was then the share price would be far, far higher. This patented tech needs to show efficacy and we can speculate about it here for days on end but the fact is that no one knows until Q1 2023 if this tech is going to be marketable.

Astellas won't initiate a Phase 2B in Europe or Asia if FX-322 is not considered a marketable proposition. They then have no obligation to fund Frequency Therapeutics under the collaboration agreement above (no milestone payments due). However if FX-345 is successful in Phase 1B, then there could be a new deal. All speculation but there is a reason the share price is as low as it is. The results for FX-322 Phase 2 were terrible and way below expectations.

The next 18 months is shit or bust in my opinion for Frequency Therapeutics as a company. Hopefully trial results are outstanding.

I think Astellas will initiate a Phase 2B if Frequency Therapeutics' Phase 2 FX-322 -208 trial brings marketable results. It is all about commercial opportunity.

We will see if poor trial design was the reason for the last Phase 2 bombing. Frequency Therapeutics seem confident but they were also super super confident pre results from last year.

 

You would need to view the subject MIT patent portfolios before we could continue this discussion.

Also, there's a different MIT consulting group for FX-322.

I had mentioned early on why failure was probably seen on the main Frequency Therapeutics thread, but I've never been a close follower of their studies. Most of my updating came from a MIT friend, who's now retired. I do understand the beyond science and concerns.

More interested in the financial/trading aspects and medical patents. My education and experience are in both medical and finance/economics. Traded medical stocks and others for over 55 years.

I rather just talk to those here with a physical health concern, as I got severe hearing loss tinnitus (sharp downward slope like yours), somatic and pulsatile tinnitus and severe pain in five body areas.

Take care.

 

Ok. I get the hint. I have middle ear myoclonus and had tenotomies of both ears, which resolved, pre-existing pulsatile tinnitus or more correctly 'rhythmic tinnitus'. I have moderate hearing loss and I presume 'normal' tinnitus. I've been an investor in various stocks for 20 years and my education is a commerce degree and Masters of education. I also worked in finance/banking prior to being a business/economics/accounting teacher. Maybe, more in common than you think but I am only 46. I've also had 23-week premature twins, and recently lost my father to a long illness, so I know all about health concerns (apart from my ow, try insomnia related sleep induced psychosis for size, not pretty I can tell you... and started all my shit). Insomnia will get you when you have two children and a father all on ventilators at one time, especially my 500 g babies... but all in perspective really... look to Ukraine/Yemen, etc to see what others go through.

I've really had more than enough experience of hospitals these last four years and you learn a lot when are on the ground so to say. I have no knowledge of medical patents but a general interest in futurology and the coming 'health' revolution.

I sincerely hope your struggle it not as bad as it seems written above. I just finished watching season 4 of Goliath and it is based on the opioid epidemic. Hopefully more viable treatments for pain will come soon.

Interestingly my crazy somatic tinnitus resolved 90% in one ear (the same one as pulsatile), after my Tensor Tympani and Stapedius were lasered and about 70% in the other ear after the second surgery. Those percentages being my ability to modulate it somatically.

As regards to Frequency Therapeutics, I feel it is a huge risk at the moment and I sold my position to offset capital gains late last year.

I would not purchase these shares now given the uncertainties, but as with all stocks there are short term trading opportunities. I don't do trading.

If FX-345 is awesome I will jump back in straight away.

Anyway, best of luck in your health struggles and hope profitable investments compensate for some of your pain.

 

I speculate we will see minor audiometry improvements for FX-345 in the 4 kHz & 6 kHz range. Maybe 10 dB or 20 dB. There is much more "square footage" in the cochlea dedicated to each frequency in the lower range which hopefully will translate to more hair cells uptaking successfully and a higher chance of seeing some audiometry improvements.

 

The deal does extend to FX-345, Astellas already has the rights to it.

The milestone payments will only payout when Astellas doses their first patient in a Phase 2b in Europe or Asia so it may be some time before any payments could potentially come in after 208 trial data releases.

 

Do Astellas still need to do Phase 2b phase in EU if the drug passes the Phase 2b in USA?

 

Do you have a source or link to that please?

 

Yes. It may not be as involved as the Phase 2B in the US, because EU drug regulating bodies can accept FDA-approved data. I am speculating that Astellas won't proceed with a Phase 2B until Frequency Therapeutics has "de-risked" the clinical trial model for their drug in the US. If the FX-322 Phase 2B trial model (and likely similar for FX-345) produces positive outcomes, the risk for Astellas lowers significantly; and they may be persuaded to proceed with a similarly modeled trial in the EU/Asia.

 

Frequency Therapeutics patents:

Patents Assigned to Frequency Therapeutics, Inc. - Justia Patents Search

Many associations, formalizations, endorsements and alliances between MIT and Frequency Therapeutics provided patent license agreements.

Exclusive Patent License Agreement, dated as of December 13, | Frequency Therapeutics, Inc. | Business Contracts | Justia

Besides compositions, MIT has a lock on procedures needed by Frequency Therapeutics with a large patent library.

Because of all this, there won't be many other development mentors, besides Frequency Therapeutics and Otonomy.

I'm sure many have knowledge of FDA guidelines. The basics:

Development & Approval Process — FDA

Frequency Therapeutics may have to redesign, but institutional investors haven't abandoned, and they won't with what is stated above - patent and procedure hope. Institutional has over 50% ownership and if needed they will increase ownership to 95%. They will also buy new share offerings to raise cash for company if needed.

I own two hundred shares (pocket change) only because one of my conditions is terminal.

Today my stock portfolio did well.

All my stocks today with the exception of FREQ and OTIC increased 16% to 80% with an average of 48%.

So, wife and self - own two hundred shares of Frequency Therapeutics because we care about those with hearing loss and tinnitus.

 

Page 28 of the most recent 10-K:

"Under the Astellas Agreement, Astellas has the right to market and commercialize FX-322 for the treatment of SNHL, and any other products containing both a GSK-3 inhibitor and an HDAC inhibitor if approved, outside of the United States. For any other product candidates that are not part of the Astellas Agreement, we intend to establish marketing and commercialization strategies for each on a case by case basis."

https://investors.frequencytx.com/node/8296/html

 

Ok that is interesting. The more potent GSK-3 inhibitor with Sodium Valproate does fit within the original scope of the original agreement. Not sure if that is good or bad thing from a funding perspective as regards to milestone payments.

One thing for sure is that FX-345 is very exciting, and could be the drug we were all hoping FX-322 was. I'm way more interested in FX-345 Phase 1B than FX-322-208 trial. I'm sure Astellas are too.

Frequency Therapeutics is poised for a takeover by Astellas if FX-345 is a blockbuster.

$42M private placing in July 2020 was at $18 per share. IPO was at $14 per share.
$545M - $80M = $465M remaining in milestones. That would equate to about $13 per share.

A buyout based on very promising FX-345 results makes complete sense. Anything north of $20-$25 per share should do it.

All wild speculation of course, but I'd love to see this project funded without doubt.

 

I highly doubt FREQ would be willing to sell for such a low amount. Their technology is a platform and isn't just limited to hearing.

Their FREQ-162 compound looks extremely promising that has a high chance of success since we know that PCA works for MS based on all the clinical trials performed by other companies and institutions over the last few years. They've outperformed Rogaine in growing hair back on mice, they've also had success in the lab in rodent ex vivo & in vivo plus human ex vivo for muscle regeneration, osteoarthritis and GI disease. The more areas we see PCA working in one part of the body, the more likely it is to also work in others. Its a safer, simpler and cheaper form of regenerative medicine compared to most gene and cell therapies out there today.

Their patents in hearing alone can be extended out to 2042 and their hearing compounds alone have the chance to pull in billions upon billions in revenue over the next 15+ years. The company has said that they intend to develop into a fully fledged biotech company, growing their own sales team and even bringing manufacturing in house eventually. If Astellas wants to buy them, they are likely going to have to shell out a few billion dollars which would put the share price closer to $100+ a share.

 

I hear ya buddy, but the share price is at $2.45 and investors are not happy about that. It is not like the company is in a strong position funding wise and has limited options. It is going to take a hell of a lot of cash to take any of their promising compounds to market. It will also take a hell of a lot of time. Where will that cash come from?

Any further equity offering will be heavily discounted and bring huge dilution.

I'm just banging the same drum here but it's falling on deaf ears. From an objective point of view I'm looking at a company that is facing huge obstacles.

The FX-322 results last year were shit. Let's face it. We all had built up hopes of a multi dose regimen penetrating deeper into the cochlea, which is what was/is needed for this drug to be marketable. The market hated the results and the share price tanked on the news. The market does no hold much hope for FX-322.

From my own experience I can tell you two things. I recently lost approx 10 dB in both ears at 8,000 Hz due to surgery. Do I notice a difference? No is the answer. I also own two pairs of hearing aids. Oticon More 1's and Phonak P90's. The Oticons go up to 10,000 Hz and the Phonaks 8,000Hz. Guess which hearing aids I wear the whole time... The Phonaks.

FX-322 is not going to be a marketable drug in MY opinion (just mine), but the market seems to agree with me.

FX-345 on the other hand could be a blockbuster.

I am consistently pointing toward funding.

To get where they are now they have burned through

$136M in series A, B and C financing
$84M IPO
$2M DOD Grant
$42M private placement
$80M Astellas

That is $344M of which they have $142M remaining.

The company has a market cap of $75M. Where will the cash come for the necessary clinical trials if Astellas thinks like the rest of the market and FX-322 is not a commercial grade product?

FX-345 needs to deliver big imho and hopefully will.

To expect a takeover in the billions is light years away from the current situation. The stock price 100% confirms that regardless of your own or my own opinion.

Anyway, I've more than said enough on funding issues so I'll park it for now. Hopefully the trial results will bolster the share price significantly before end of 2023.

Just in case anyone thinks I am 'shorting' the stock or being overly negative, I am one of the 'ideal candidates' for FX-345 and have a huge interest in it succeeding. I was very strong in my belief prior to Phase 2 results last year and was very down after the results. Here is a picture of my audiogram as proof. I will continue to be a contrarian voice on here. It is needed. The company have been overly enthusiastic with their PR in my opinion. I do believe in Bob Langer though. PCA is showing great promise and gives us all hope.

 

Almost 80% of the companies of the Nasdaq Biotech Index (NBI) companies have no earnings with over $250 billion in market capitalization. Pipeline often justifies a part of the value of a company. So, when I see a biotech quarterly results with no sales, I place some of the emphasis on the progress of its drug development.

In trying to judge a biotech worth, I include messing around with risk-adjusted value," or RAV, for the entire company pipeline.

The formula for RAV looks like this:

RAV = Market Potential "unmet need" * Market Share * Likelihood of Approval (LOA)

First, I try to calculate the value of each drug by multiplying its market potential by its projected market share. This calculation gives the value of each drug assuming approval.

I then adjust for risk that the drug will not pass-through regulation by multiplying the value of each drug candidate by its likelihood of approval (LOA). This gives me the risk-adjusted value (RAV) for each drug, which can be added together to determine the total pipeline value of the company.

Obviously, things like likelihood of approval and market share will be difficult to put a number on, as it gets a little tricky. I haven't attempted to find value or RAV for a biotech since I become disabled.

I had fun trading biotech by telephone in the 80s when there was less competition.

My favorite companies of days gone past:

The Boston Celtics that also had a very large dividend and I got free Celtics logo stuff.

Warner Communications - Atari.

Topps (sports cards) - got a special dividend of $1 per share.

 

And fortunately, management & all the co-founders of the company flat out disagree with you. They say FX-322 is a very promising clinical candidate and I will take their opinion over yours. An article just came out of MIT this morning and here are a few great quotes from it:

"Some of these people [in the trials] couldn't hear for 30 years, and for the first time they said they could go into a crowded restaurant and hear what their children were saying," Langer says. "It's so meaningful to them. Obviously more needs to be done, but just the fact that you can help a small group of people is really impressive to me."

For now, Karp is already thrilled with Frequency's progress, which hit home the last time he was in Frequency's office and met a speaker who shared her experience with hearing loss.

"You always hope your work will have an impact, but it can take a long time for that to happen," Karp says. "It's been an incredible experience working with the team to bring this forward. There are already people in the trials whose hearing has been dramatically improved and their lives have been changed. That impacts interactions with family and friends. It's wonderful to be a part of."​

But I know they don't mention audiograms so most everyone on Tinnitus Talk will consider it "trash results".

As for cash, you do realize that the stock price is not locked in at $2 a share for the rest of time? They have enough cash on hand to get them through to new Phase 2b results and FX-345 Phase 1 results. Management has repeatedly said that the failed trial was not due to the drug and it was due to trial design. The trial would have passed with flying colors if they didn't have the unprecedented placebo response. Once the new Phase 2b data drops for FX-322, I expect the stock price to recover some and then they will be able to issue more shares to raise capital with much less dilution but you don't seem to believe there is any possibility of that ever happening so I don't know what more to tell you.

The company hasn't been over enthusiastic about their PR, they've been quite open to the world about how they are conducting their science; much more so than most other biotechs. It's just that the desperate people who want solutions will be disappointed with anything that doesn't restore them back to perfect hearing.

So, if FX-322 gets FDA approval, can I assume you won't be taking it then?

 

You think the first hearing restoration treatment is not marketable?

 

It's not just audiograms, they're doing word clarity and words-in-noise tests too, and nothing has been that impressive so far. Data is king and if Frequency Therapeutics can't produce good data then none of these feel good stories matter - they could all just be due to the placebo effect.

This is super important though. The question is - why was there a placebo effect? People could have lied their way into the trial with fake WR scores, but they had more of a chance of landing in an FX-322 group than a placebo group. Were there outliers in the placebo group that led them to think this? Or did everyone in the placebo group do well?

It could be that people actually are capable of "squinting" their hearing, or it's possible the gel they're using does some kind of "cleaning" while it's in the ear that leads to a very minor hearing improvement. Whatever the case, improving over a placebo is the most important part of a drug's performance. If it can't do that, then its effect probably isn't real.

That seems really high. Spending a billion on promising Phase 1b results? FX-322 had promising Phase 1B results and people now have the hindsight of FX-322's Phase 2a in their subconscious. Plus, if FX-322 fails, Astellas wouldn't need to pay much of a premium because Frequency Therapeutics would already be low on capital and would have to majorly dilute to raise money.

I think the best scenario is still FX-322 clearing the bar for efficacy and them diluting to raise some more capital. Buyouts could cause drama and disrupt the process of quickly bringing the drug to market.

 

Yes I do, and so does the entire market. Why the hell do you think the share price is down 90%+ from an all time high of $55 to c. $2 based on Phase 2 of this first hearing restoration.

I know this is a hearing loss drug and forum but maybe you need LASIK. BTW, LASIK is a nice comparison of a tech that completely restores function at a reasonable and profitable price.

You do realise that most sounds are in the sub 8,000 Hz range, don't you, with a few extending into 10,000 Hz, but above that the amount of sounds is minimal.

What does FX-322 do??? Does it completely restore hearing? Look at my audiogram and tell me why I am not excited at all about FX-322. No one is. The share price reflects that. It does not hit any of the sub 8,000 Hz sounds so why the hell would I pay for it.

You are the clown buddy if you think FX-322 results were good. They simply were not. A 90% decline in share price is solid EVIDENCE that they were not. Go back on the posts after the release of February 2021. Total devastation.

Try to think objectively here and not romance the tech before it is mature or shows efficacy in a range of hearing that people will gladly pay money for.

Why have Astellas not initiated a Phase 2 in Europe and Asia if this FX-322 is going to be the goldmine you think it is?

It quite simply does not do enough as regards hearing restoration to become a commercially viable product.

That is as plain as day. Based on existing evidence.

FX-345 is a totally different proposition if it restores hearing in the zones where people ACTUALLY HEAR SOUND.