Frequency Therapeutics — FX-345

Well, this thread can be shelved. FX-322 and FX-345 are both done.

Frequency Therapeutics Announces Topline Results for its Phase 2b Study of FX-322 for the Treatment of Sensorineural Hearing Loss

"The Company will now discontinue the FX-322 development program. In addition, while dosing of FX-345, a second program to treat SNHL, has been completed in the initial safety cohort of an ongoing Phase 1b trial, that development program will also be discontinued. The Company will now focus its resources to advance its remyelination in MS program into the clinic."​

 

The cancelling of FX-345 was the only thing that shocked me with today's press release. I had kind of expected FX-322 to fail again. The data from the previous studies wasn't great, and was in fact it was weaker than Otonomy's OTO-413 data, so I felt there was a good chance it would either fail, or if it did succeed, the benefits would be very minor.

The fact that they're shuttering FX-345 too means they've lost complete faith in their hearing tech. It makes me wonder what the problem with these drugs was. Are they not regenerating human hair cells? Are the hair cells not connecting up properly? Is the drug not being delivered properly? Maybe there's another piece to the hearing puzzle that we're not aware of yet?

 

I was banking more on FX-345 working, FX-322 seemed like a long shot. Hopefully their MS drug works, there's way too many people who suffer from it. Then maybe they can return to hearing restoration with a load of cash to do so.

 

FX-345 did seem like the better product.

I wonder why they dropped it so easily?

 

Doesn’t make any sense but I’m guessing they didn’t reach the 40% success rate.

 

I think it was the same formulation, just in a different solution to permeate further. Basically it's the same active ingredients in both and if it doesn't work, who cares how far into the cochlear it reaches.

 

It was not. The regular FX-322 is 88 mg/ml sodium valproate (HDACi), 3.1 mg/ml CHIR99021 (GSK3i), 5% w/v DMSO (solvent for CHIR) and 16.1% w/v Pluronic P407 (gelling agent). FX-345 is likely (based on very limited info they released) the same 88 mg/ml sodium valproate, 5% w/v DMSO and 16.1% w/v Pluronic P407, but the GSK3i is different. I suspect it is LY2090314, or its derivative. It is about 20 times more potent than CHIR.

They could have reached further down the cochlea with CHIR, but they had some limiting factors. For example, if one adds more sodium valproate to the solution, the formulation gels above body temp, instead of at. One way to counteract that is by purifying the polymer (P407), i.e., removing the low molecular weight strands, thereby letting the regular long strands gel at a lower temperature. With this method they could reach 130 mg/ml of sodium valproate concentrations, possibly enough to reach down to 7-8 kHz instead of about 10 kHz with regular FX-322. CHIR also had a solubility limit of around 5.1 mg/ml, so that was another problem, hence the new GSK3i. Another problem with higher sodium valproate concentrations is the high tonicity of the solution (lots of salt ions). The regular FX-322 is hypertonic as-is, and that can actually lead to hearing loss when applied to the cochlea, in my opinion.

 

@Tau, how did you get acoustic trauma at 110 dB?

 

Headphones, I could not hear the sound for some reason. Increased the volume, still could not hear it. But it did damage.

 

They've already dosed several people with FX-345 and they're not going to collect any data. How much more money does it take for a few hearing tests on a handful of people? Was that really going to break the bank?

 

So sad. Can there be som good news soon, please?