Pipeline Therapeutics

If I had no hope, I’d be dead 100%.

 

I hope we see PIPE-505 getting positive results. If so, it would put PIPE-505 and FX-322 around the same timeline. I hope they move onto the next Phase ASAP so these drugs can come out into the market and help us.

 

It will be interesting to see what this drug can do. OTO-413, a competing drug for synaptopathy, had promising results in its Phase 1 on similar outcomes.

If outcomes are positive, I would anticipate Pipeline Therapeutics moving to Phase 2 as quick as possible.

 

I was really disappointed that OTO-413 had positive results but they decided to repeat Phase 1 again. I hope if PIPE-505 gets positive outcomes that they move onto Phase 2 as quickly as possible.

 

I actually think Otonomy did the right thing for OTO-413. By extending the Phase 1, they're going to get a better understanding of the type of patient that OTO-413 will benefit the most. This will help expedite the development, and hopefully recruiting for a future Phase 2. Ultimately, the extended Phase 1 may help shorten the timeframe getting OTO-413 to product.

As for PIPE-505, we'll see what happens. If PIPE-505 is anything like Audion Therapeutics' drug, it might be disappointing. However, if it looks successful, they'll need to recruit the staff and funding necessary to presumably conduct a Phase 2A / B?

 

I didn’t know that OTO-413 could come out sooner with an extended Phase 1 trial.

With the extended trial, are they going to be giving participants a higher dosage?

I think with PIPE-505 they said that there was minimal supporting cell loss. Hopefully one of these drugs that come out in the market work for getting rid of hyperacusis.

Someone who gets these drugs first will be able to let us know which conditions improved.

 

I believe all new participants are getting the higher dose. The more I come to learn about synaptopathy, the more I begin to think that synaptogenesis should provide some relief to the varying symptoms of “hyperacusis.”

 

My personal belief is that reactive tinnitus (at least how I experience it) could be occurring as a result of synapse damage. If degraded synapses lead to hearing difficulties when presented with noisy environments, it would seemingly make sense that tinnitus would elevate in the presence of noise, especially since there would be less auditory input in those instances.

 

With the timeline between PIPE-505 and FX-322 being the same, there's a good chance that they could come out at the same time. Hopefully there are no more additional delays.

 

I have thought the same thing recently. I believe in the OTO-413 thread, a video was shared of a presentation about synaptopathy. In that video, the researcher/presenter described how different synapses on each hair cell provide the brain with different types of signals. In his example, when referring to hearing-in-noise deficits, he described that certain synapses provided very "fine tuned" signals to the brain, while others gave more sweeping "wide band" type signals from the same hair cell. These signals, when differentiated are believed to provide the brain with the information to distinguish information in a noisy environment. So, as these synapses degrade, one might conclude that if there is enough degradation across the cochlea, the brain's ability to get the correct mixture of fine and wide band information would make "decoding" receiving useful information much more difficult, if not impossible.

When I consider that it is believed that tinnitus and hyperacusis may result from perhaps extreme cases of synaptopathy (I myself had observed hearing-in-noise difficulties about a year before my tinnitus and hyperacusis set in), I think of a cochlea where perhaps there are large areas of completely missing synapses, and what cells are synapsed are providing maybe only the wide band or fine tuned signals. So, the brain has to work with very sparse and limited information; which it would make sense if the wideband signaling is all that remains, that the brain would have a tough time decoding when to turn things down when they aren't actually too loud, or how to compensate for a signal when neighboring cells arent proving a signal at all.

Just a #DieselTheory... so who knows... I am definitely optimistic that reversing any damage is going to reduce the symptoms associated with hyperacusis.

 

I’m grateful that the timelines of both FX-322 and PIPE-505 are the same. Some of us may need a synapse drug like PIPE-505 whereas others with hair cell loss may need FX-322.

If PIPE-505 ends up being successful, do you see them allowing shareholders to buy their stock? Wouldn’t Pipeline Therapeutics need to get funding from somewhere to complete these trials?

 

Looking at the ClinicalTrials.gov website, I wonder if they mean the trial officially ends in June, but the results aren't released until later. This waiting game just eats you up inside.

 

They have to analyze the results.

 

Do you know when the results will be released?

 

Since the etiology of hearing disorders is so poorly understood, it seems like we might just need to try everything we can get our hands on as soon as treatments become available.

 

No idea. I’m sure they will make some announcement.

 

Neither PIPE-505 nor OTS-413 are letting people into their trials who have "bothersome tinnitus". To someone waiting for a tinnitus cure, that seems like a bit of red flag.

 

They aren’t testing for tinnitus using a tinnitus measurement, why include them?

 

What if those with tinnitus were the only ones able to benefit from their synapse drug solution? I guess we’ll never know with their restrictive trial criteria?

 

Tinnitus should be a neutral factor in this case. Why exclude people with tinnitus while it’s known tinnitus often comes with hidden hearing loss and cochlear synaptopathy?

 

I have some theories.

It’s possible they don’t want people with “bothersome” tinnitus because it’s also measured as a safety outcome. So, if someone already had bad tinnitus and the drug made it worse, that might be hard to capture. If they didn’t have it all, and got tinnitus, it would be easy/more accurate to measure.

I also tend to believe people with bothersome tinnitus might be an attrition problem for the study. If you got placebo or drug and your tinnitus got worse, would you return to the follow up visits or drop out? I look at the number of people getting way anxious about the COVID-19 vaccines as an example of patient bias. Drop outs don’t make the study look good.

It’s also possible that they might believe that patients with bothersome tinnitus may affect the trial outcomes because let’s be honest, there is a lot of desperation to get a drug for tinnitus.

 

From their perspective, maybe it is just considered a complicating variable without upside since they aren’t testing for it.

 

We've been trough this before...

 

Hope so man. Hyperacusis is terrible and hopefully it eliminates TTTS and ear spasms, the facial nerve pain I get from it is insane.

 

When will the trial results be released?

 

I heard anytime now.

 

Where did you hear that?

 

On ClinicalTrials.gov it has the estimated completion date of the study as June 2021.

 

Yes, I know what ClinicalTrials.gov says. But we don't know if Pipeline Therapeutics plans to release the results this month. We haven't heard anything from them.

 

I've been digging around trying to find clues about how the results of this study may turn out. I found an article from last year that had an interesting quote from their CEO: [1]

The dual mechanism of action for PIPE-505, involving repair of the cochlear synapse and the regeneration of outer hair cells critical for hearing quality and sensitivity, uniquely positions this small molecule to address two of the main cochlear elements commonly lost in SNHL​

The chart I showed in the OTO-413 thread indicated that the loss of synapses and OHCs seem to be the main reasons for age related hearing loss (and SNHL too). Since this drug addresses both of those, I wonder if we could see blow out results from this first study?

However, I have some concern that it's taking them so long to release the top-line results. In that article they were expecting to release the top-line results "early 2021". Their study is small, involving only 24 patients and 90 days. I can't imagine recruitment was that hard. Additionally, they raised money in February, which I find concerning. If they were confident in the results, why not wait until afterwards to raise money? Surely they'd get a better deal if they had good results.

Also, I saw that they were delivering the drug via an intratympanic injection. Anyone know if they have a special time-release gel like Otonomy?

[1] Pipeline Therapeutics Initiates Phase 1/2a Clinical Trial of PIPE-505 in Sensorineural Hearing Loss