Pipeline Therapeutics

Found this announcement today:

https://www.businesswire.com/news/h...Participate-Stifel-2019-Healthcare-Conference

Here is their official website:

https://www.pipelinetherapeutics.com/

It appears to be a relatively new biotech company. Of note, Stefan Heller is on their advisory board.

The news article lists their candidate PIPE-505 as another gamma secretase inhibitor but for cochlear synaptopathy rather than hair cell growth.

From their website, they may actually have two separate compounds for synaptopathy about to start phase 1, however.

 

Wow. Very interesting. Looks very promising. Nice find.

 

“A Phase 1b/2a study of PIPE-505 in SNHL is expected to begin enrolling patients in 4Q 2019, with topline results expected in late 2020”.

Here’s hoping that one of their exclusion criteria isn’t tinnitus.

 

So a combined phase 1 and 2 study? Interesting.

Also, what indication would they even have that you had cochlear synaptopathy? Speech in noise? Wouldn't tinnitus be a prime indicator?

 

Speech in noise is a primary indicator, yes.

Hopefully there will be an online transcript of the CEO's 11/20/19 conference talk and it will include study inclusion criteria.

 

From what I understand yes, difficulty hearing speech in background noise is the predominant indicator of synaptopathy. However, some companies seem very concerned about eliminating variables in their trials (as we’ve seen with Frequency Therapeutics) and tinnitus often seems up on the chopping block.

OTO-413, currently the only trial available for cochlear synaptopathy, made it very clear to me that “bothersome tinnitus” would exclude me. It’s very frustrating, and I’m hoping Pipeline Therapeutics will not follow suit.

 

Great find and another sign things are moving in the right direction for hearing loss. Interesting they’re focused on mild to moderate hearing loss due to synaptopathy. I had no idea you could get up to moderate hearing loss from that.

 

Looks like their patent specifically mentions tinnitus, too:

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018111926&tab=PCTCLAIMS

 

That’s great news!

 

Thanks I was looking for that.

It says IT injections. Hope it can get over the delivery hump.

 

Two questions that come to mind:

1. What is their other eardrug, PIPE-336, intended for?

2. Is Phase 1b/2a snake oil tongue for Phase 1/2?

Hope this doesn’t become Pipedream Therapeutics.

 

Whats interesting that if you open their presentation from the 49th Chicago Neuroscience conference you’ll see that PIPE-505 not only cured synaptopathy but ALSO regenerated hair cells.

Curiously enough PIPE-336 was missing from this presentation. They will be attending another conference next week so maybe we will get more information then.

 

Robert Jackler at Standford said that regenerating hair cells restored synapses. It seems like all of these things are related.

 

So FX-322 and Regain/Audion should do the same thing as well?

 

We don’t know if those drugs can regrow synapses of hair cells that remain in the inner ear. The new hair cells those drugs regrow probably do have synapses. If I’m not mistaking Pipeline’s drug primarily intends to regrow synapses that were damaged without loss of the hair cell.

 

Do you believe that if these drugs did work would we basically have our ears before we had tinnitus and hyperacusis or do you think we would be more easily susceptible to damage even if it did get rid of our tinnitus and hyperacusis?

 

I think they already found out there’re genetic components to hearing loss. By that I mean not genetic deafness or anything, but genes that make you more susceptible to hearing loss during life. These drugs are not going to solve that.

 

If that’s what people are worried about once this curse has been lifted, take Pramipexole and get on with what’s been left of your life.

 

Looks like they have updated their website. No longer mentions PIPE-336.

 

I have some more information. Of interest is that this compound is not just comparable to NT-3, but is supposed to be more potent. The finish line is getting closer and closer.

@JohnAdams youve wanted your NT3 human trials, well you’ve got em now :33

———

I received your emails and can try to answer your questions here.

• Regarding NT3, yes, we followed the protocol used by Charles Liberman and find that PIPE-505 is more effective at restoring synapses in models of cochlear synaptapthy. We are very excited about these results and have filed an IND with the FDA to test this compound in patients with NIHL associated with cochlear synaptopathy.
• Yes, PIPE-505 is able to penetrate throughout the cochlea from the apex to the base. We have conducted extensive inner ear pharmacokinetic experiments to demonstrate this exposure.
• To your question around tinnitus. I am familiar with the suggestion that some forms of tinnitus may be caused by cochlear synaptopathy. We have no direct evidence for or against this claim. We will not be testing our compound in tinnitus patients under our current IND but this is something we could explore in the future.

Upon asking about tinnitus as an exclusion factor:

Tinnitus may be an exclusion factor. I would need to check in with our CMO. More importantly, we will be trying to enroll patients with mild to moderate bilateral hearing loss (no more that 40dB hearing threshold) who also have evidence of cochlear synaptopathy by word in noise test or speech in noise test.

Also it is definitely confirmed that it will be a phase 1/2 combined trial. And that they have seen benefits for ototoxic induced synaptopathy as well, not just noise induced.

No recording of their presentation unfortunately :/

And while I know they say they have no direct evidence in synaptopathy being the underlying cause of tinnitus, I think the fact that tinnitus is included in their Delivery Patent isn’t JUST pre emptive. I don’t think they would include it in there as a passing fancy.

 

My main gripe about that stuff is that it would need to pass extensive safety trials and then efficacy trials, and I know the world doesn't know that it is safe, but I do, so to have to sit and wait for the government to verify something I already know is just maddening.

 

Totally get it, but I know we all thought Decibel would have started this years ago so it feels like the gears are finally starting to turn. They should have turned 10 years ago, and it drives me crazy that all we can do is sit on our hands until these trials are complete, but the fact that they are combining safety and efficacy is heartening. It condenses this maddeningly long time line even just a little bit.

 

Until this treatment gets available to the public, and we can assess its efficacy, this is more in the line of "pipe dream therapeutics". (Pun intended)

 

Sadly, even if this does restore synapses perfectly, tinnitus may need a multi faceted approach. New hair cells, new synapses, and sound therapy.

 

Sound therapy? You mean bimodal neuromodulation right?

 

No, just sound therapy. I'm not saying nueromodulation wouldn't be good too. I have zero experience with that so I cannot say.

 

Well, this would explain why some participants at FX-322 phase 1/2 trial had their speech-in-noise parameters improved after the injection!

 

That's amazing if I properly understand past comments related to other drugs whose penetration throughout the cochlea is a stumbling block. Have they devised a new delivery method or is there something about this drug that simply diffuses more thoroughly.

Great development regardless.

 

Per their patent, it looks like they are using a aqueous formula with poloxamer 407. This is what Otonomy uses for their sustained release intratympanic Dexamethasone (per PubMed). Obviously if it's for Meneire's patients (Otonomy's Dexamethasone formulation I mean) it would have to diffuse to Apex or wouldn't be very useful for Meniere's. It follows that Pipeline's drug should have good penetrance there, too.