Oricula Therapeutics Hopes to File for FDA Approval This Year

[Samir]

Oricula Therapeutics appears to be preparing for an FDA filing for drug approval. But I could not find any clinical trial results.

A new drug in development could avert permanent hearing loss associated with some chemotherapies

Fred Hutchinson Cancer Research Center medicinal chemist Dr. Julian Simon and his colleagues at the University of Washington used the tiny, silvery fish — many, many thousands of them — to find a drug that they think will prevent the hearing loss that often accompanies treatment with certain chemotherapies or antibiotics.

The chemo and antibiotics also kill fish lateral line hair cells, and it's easy to quickly check for the loss of those cells under the microscope, making these tiny animals a good starting ground for research to prevent that drug-associated hearing loss. Simon, an expert in screening large numbers of potential drugs in the laboratory, teamed up with UW zebrafish and hearing researchers Dr. David Raible and Dr. Edwin Rubel to screen different molecules that could, if given in the water that the fish are swimming in at the same time as the chemo or antibiotics, cancel out the associated hair cell-loss.

After 10,000 tests, they found one.

That compound, which the researchers termed PROTO-1, led to the creation of a spinoff company, Oricula Therapeutics, which is developing an optimized version of the drug for clinical trial testing. The company hopes to file for approval with the Food and Drug Administration this year, Simon said.

Ultimately, the researchers hope to test the drug in other types of hearing loss, including age-related hearing loss, which affects nearly half of people over the age of 75. That would require fairly massive and lengthy clinical trials though, Simon said. But still, it's a pressing concern.

https://www.fredhutch.org/en/news/center-news/2017/06/preventing-chemo-induced-hearing-loss.html

 

[Aaron123]

Oricula Therapeutics appears to be preparing for an FDA filing for drug approval.

It appears that this refers to an IND application rather than an NDA. Assuming the IND (Investigational New Drug) application is approved, they will be able to start clinical trials. At the other end of the process - after a Phase 3 trial, they would submit an NDA (New Drug Application).

There's a thread from last year about Oricula though it is important to note that "Phase 2" refers to the SBIR program, not clinical trials: https://www.tinnitustalk.com/threads/new-phase-ii-grant-for-oricula-therapeutics-llc.13842/

 

[Samir]

It appears that this refers to an IND application rather than an NDA. Assuming the IND (Investigational New Drug) application is approved, they will be able to start clinical trials.

Yeah, you are right. I e-mailed them about it. This is their response.

We are currently just finishing preclinical testing and should be moving to human testing next year - initially just normal volunteers. We [are] hoping to show hearing protection against aminoglycoside antibiotics the following year.

If I interpret this correctly, they will be filing an IND for a Phase 1 clinical trial this year. Whether or not they will get approval, when they will get approval, when the actual trial will start... that, we don't know. Assuming everything goes according to plan, that will all happen very soon.

It seems to me like they hope to get the results in the following year, and show efficacy. But I'm not so sure about this, because they need to first complete the Phase 1 (in "normal" volunteers"), then the Phase 2 and get the results in from that one, before they can show efficacy.

In summary:
2017-07-01 – 2017-12-31: File IND
2017-07-01 – 2017-12-31: Start Phase 1 trial
2018: Start Phase 2 trial
2019: Show efficacy from Phase 2 trial
2020: Start Phase 3 trial

That's my estimate, anyway.

There's a thread from last year about Oricula though it is important to note that "Phase 2" refers to the SBIR program

Yeah, I saw that. I thought it was a clinical trial. But on closer look I see that the term "phase II" is used in a different context.

 

[TuneOut]

"The drug that's come out of all these studies, known as ORC-13661, is about 100 times more potent than PROTO-1 and actually works (in animals) to prevent both antibiotic- and cisplatin-related hair-cell loss."

Anyone know the names of the actual chemical compounds? I searched everywhere and couldn't find any info. Is it related to d-methionone?

EDIT: Nevermind, I see they just screened a ton of small molecule drugs for activity.

 

[Samir]

Nevermind, I see they just screened a ton of small molecule drugs for activity.

Yeah, they screened like 10,000 molecules. I did not see any reference to any chemical name. They will probably not reveal that until later.

This is not as exciting news as I had hoped. But it's definitely a step in the right direction.

 

[Samir]

From an earlier news article from 2016:

According to CEO Malcolm Gleser, Oricula expects to have collected enough data to ask for Food & Drug Administration permission to begin human studies of the drug in the fall of 2017.

http://cen.acs.org/articles/94/i11/Drugmakers-tackle-hearing-loss.html

I hope they meet their target. There is definitely a lot of activity now in the field.

 

[jer]

This is VERY exciting news!!! Just think of how many people this will help for their tinnitus not to get massively worse, or to even get it at all. I am so happy that they are finally about to go to trials. This is a very good day!

 

[Autumnly]

A Clinical Trial for a New Drug to Protect Hearing
The U.S. Food and Drug Administration (FDA) has approved a novel drug to protect against ototoxicity (harmfulness to hearing) due to the use of aminoglycoside antibiotics to treat severe infections. The FDA approval paves the way for a Phase I clinical trial to test whether the drug, found to be significantly protective in animals, is safe for humans.

 

[Samir]

How is it going with that trial? Have they not started it yet?

I found these two articles in the Journal of Medicinal Chemistry:

Mind Your Ears: A New Antidote to Aminoglycoside Toxicity?
https://pubs.acs.org/doi/10.1021/acs.jmedchem.7b01645

Phenotypic Optimization of Urea–Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss
https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.7b00932

 

[Autumnly]

Decibel Therapeutics and Oricula Therapeutics Announce Exclusive License for ORC-13661 in Phase 1 Development for Hearing and Balance Protection

A new hope for patients facing irreversible ototoxicity resulting from the use of an important class of antibiotics

Boston, Mass. and Seattle, WA, September 27, 2018 – Decibel Therapeutics and Oricula Therapeutics today announced that Decibel has obtained an exclusive, worldwide license to the development and commercialization of ORC-13661, an oral medication developed by Oricula Therapeutics for the prevention of hearing loss and balance disorders that can occur following treatment of severe infections with aminoglycoside antibiotics. Particularly susceptible populations include those treated for pulmonary exacerbations associated with cystic fibrosis, non- tuberculous mycobacterial infections, multidrug-resistant tuberculosis, and endocarditis. As part of the agreement, Oricula will provide ongoing scientific advice and support.

With roots in a research collaboration between the University of Washington and the Fred Hutchinson Cancer Research Center, ORC-13661 was licensed to Oricula Therapeutics in 2013 to accelerate preclinical research activities and advance the compound into the clinic. A Phase I clinical trial to evaluate safety, tolerability and pharmacokinetics is currently ongoing.

About ORC-13661
ORC-13361 is a new chemical entity (NCE) currently being investigated for the prevention of ototoxicity which results from treatment with aminoglycoside antibiotics. It is thought to work by temporarily blocking aminoglycosides from entering into hair cells in the inner ear, thereby preventing damage before it can occur. Two relevant composition of matter patents, valid through 2036, have been granted by the USPTO and related global filings are in process. ORC- 13661 is also referred to as DB-041.