Frequency Therapeutics — FX-345

Starting this thread on Frequency Therapeutics new FX-345 drug for Sensorineural Hearing Loss.

Here's what we know so far:

• Second clinical program focused on regrowth of sensory cells using PCA.
• Enables coverage of large portion of cochlea.
• Potential to address additional SNHL patient types (in addition to FX-322)
• Formulation enabling evaluation of a range of dose levels
• Developing in addition to FX-322, and clinical data will drive commercial positioning

What's planned so far:

• IND Submission to FDA: Q2-2022
• Clinical Study: H2-2022

 

I only saw part of the webcast. Did they indicate why they think FX-345 may help a broader range of patients?

 

Because it penetrates more deeply into the cochlea compared to FX-322.

 

Did they say how?

 

Take a look at their investor deck, or watch the R&D event, this is the extent of most of the public knowledge:

https://investors.frequencytx.com/static-files/d0fdfc76-ef0f-426b-8b15-21f4d6ffd61b

https://investors.frequencytx.com/2021_Virtual_R-D_Event

 

It says quarter 2 of 2022 for the clinical study. That's very soon. Maybe I should hold off trying to get into the current trial for FX-322. This new drug sounds much better.

EDIT: Oh wait, it says IND in Q2. So, I guess the clinical trial is not until later in the year. Fuck.

 

It's H2 2022, which means the second half of next year. That could mean they won't start for another year. Phase I studies can be risky too, I personally would wait for a Phase 2, but it's whatever you're comfortable with.

 

This is fascinating research. However, they do not even use the word tinnitus in the presentation. Realistically, when could those of us with regular old tinnitus hope to have this available to them? Also, is it me or is taking a needle in my ear utterly terrifying?

 

So FX-345 is exactly the same drug as FX-322 but goes deeper into the cochlea, am I right?

 

If you have HF hearing loss, try to get FX-322. If mid and low frequency hearing loss, then I'd think FX-345 would be better.

 

The expected outcome is the same = more hair cells. But the drug is different because the chemical makeup is not the same as FX-322. Watch Chris Loose's part:

https://investors.frequencytx.com/2021_Virtual_R-D_Event

 

I'm in the latter camp (i.e. mid/lower frequency damage all the way up through the high frequency range), but if I could get in on the new FX-322 trials, I'm thinking why not try it and see what happens - any trial is 50% chance of placebo anyway.

Would that exclude me from a later trial though? Or other trials e.g., OTO-413, also?

 

You’d have to look at their exclusion criteria.

 

So this new drug can reach around 4 kHz does anyone know how far FX-322 could reach by comparison?

 

They presented studies very early on that FX-322 reached all the way to the base with therapeutic amounts by studying people who were getting cochlear implants.

 

12 kHz according to this graphic.

 

If FX-345 could reach 20-4 kHz, then it's great, but aren't the hair cells responsible for speech frequencies below 1 kHz-2kHz?

 

Hair cells are responsible for hearing all sound frequencies. Moving from a lower limit of roughly 8 kHz with FX-322 to a lower limit of 4 kHz with FX-345 should help improve word recognition/clarity where consonants and vowels occupy the 4 kHz - 8 kHz range.

 

Inner Hair Cells: Speech
Outer Hair Cells: Audiogram

 

On the one hand I’m glad they’ve come with something new, but on the other hand I can’t help but feel “here we go again”. It’s like we’re back in 2017 when FX-322 was promising.

 

FX-322 still appears to be promising. And FX-345 appears to be building on the learnings from it. What am I missing?

 

FX-322 is still promising if you look at their data in the presentation.
FX-345 is just even more promising

 

The caution is justified, but it's like other human drivers. Fear, when you think about it, is good and necessary but in most cases panic is bad. Going all euphoric about this latest arrival should be postponed until it has been proven to be successful.

Having said that, I am much cheered to see that the wheels of research are moving again.

I think the Wright brothers took a kind of a long and a broad view when they were getting their bicycle with wings airborne in Kitty Hawk sands during the 1900s.

It's cheering as well to see how the vocabulary is expanding to make different distinctions... like instead of just saying "deaf" they distinguish between sensorineural, age-related, sudden hearing loss etc.

At least they are getting there.

It might be in you grandchildrens' time but they are getting there.

A bit like the climate change thing, you have to believe you can do it. If we didn't, we'd all be f**kd.

 

If the ingredients are different, would there be risks in getting both drugs?

Also would this new version render FX-322 obsolete or can they both coexist and serve their own purpose?

 

My hearing loss & tinnitus tone is at exactly 4 kHz. I wonder if FX-345 will help, or if 4 kHz will be to close to the edge of the drug's effectiveness zone to receive much benefit?

 

I don't see it being an issue to get a dose of FX-322 and then a few years later getting a dose of FX-345 as both drugs target the same pathways, FX-345 just happens to be more potent.

I'm betting their current plan is to get FX-322 to market first to unlock a revenue stream and then once FX-345 gets approved a couple years later, FX-322 will be discontinued and replaced by FX-345.

 

A lot of individuals do not have hearing loss below/at 2 kHz anyway who would be in the target group for Frequency Therapeutics. Thus this is why even in certain CI candidates, there tends to be an approach where they don't do anything with these lower frequencies.

From a lot of evaluations and research, it appears that the majority of individuals tend to have hearing loss to/around 4 kHz. It is also fairly probable that there will be further evaluations and/or development into another medicine which can go deeper than 3 kHz too.

 

Question: I thought the delivery method is what decides how deep any drug can penetrate, not the drug itself?

I’m happy Frequency Therapeutics is pushing forward, but looking at recent history, they have proven to be way better at talking the talk than walking the walk. Sure, good communication is advantageous, especially when it comes to keeping the money coming in, but at some point I hope there will be some properly potent, concrete results also from the medical side.

 

The purple seems to go past the 4 kHz and slowly fade out until 1.5 kHz.

 

I suspect your strategy is correct here. Get FX-322 to market and create cashflow. Then, bring FX-322 patients back in for the more robust FX-345 treatment.

And by then, there will probably be another FX-3XX in the works that goes even deeper once everyone gets FX-345.