Akouos — A New Company Focused on Genetic Hearing Loss

[Aaron123]

There's a new company - new to me anyway - focused on hearing loss. Specifically, they are focused on hearing loss due genetic defects: https://www.akouos.com/

Here's the/a press release about a licensing arrangement between Akouos and MEEI: https://www.prnewswire.com/news-rel...chusetts-eye-and-ear-and-lonza-300563920.html

 

[Samir]

Good find Aaron! You are on fire lately! Keep them coming!

 

[Makrohn]

@Benoves Check this out

 

[Aaron123]

Here's a bit more information on Akouos. They received SBIR (small business innovation research) funding this year and are developing a minimally invasive delivery system presumably to deliver gene therapy to the inner ear: https://www.sbir.gov/sbirsearch/detail/1305311

 

[Paulmanlike]

They just keep coming man, could treating hearing loss pharmaceutically (is that a word?) be the new laser eye surgery that's a multi million or billion dollar market?

Nice find Aaron, although which will come first? Treating noise induced deafness or genetic defect deafness?

 

[Benoves]

@Benoves Check this out

This one looks serious. Thanks for tagging me. Looks like not many companies are targeting this? Is this different from wat audion/frequency are doing?

Hope they wil find a cure in our lifetime, for hearing loss and tinnitus. Better be soon. Untill then i hope to habituate.

 

[Enclave]

https://endpts.com/nea-5am-back-a-5...inic-at-akouos-the-latest-startup-in-hearing/

Akouos has significantly expanded their platform profile to include multiple forms of hearing loss. This technology appears to be a robust evolution of what Genvec (CGF166) was trying to achieve.

50mil is a large series A investment to get their research to the clinic.

 

[IvanRus]

https://cen.acs.org/business/start-ups/Akouos-raises-50-million-develop/96/web/2018/08

Yes, this is another startup that managed to attract 50 million dollars of investment.
With their focus on genetic hearing loss, I have some misunderstandings, I will contact them.
Probably, they focus on a new method of regeneration - viral regeneration of hearing. They hope to launch a genetically modified virus that will restore hearing.

Reference:
Today there are 4 main directions for the possibility of regeneration of the inner ear, this is:
1) Treatment with stem cells;
2) Gene therapy;
3) Cell therapy;
4) Viral therapy.

 

[Samir]

Akouos Secures $50M for Hearing Loss Gene Therapy R&D
https://www.xconomy.com/boston/2018...secures-50m-for-hearing-loss-gene-therapy-rd/

 

[Samir]

A short promo clip with the CEO, Manny Simons.

 

[FGG]

This company is about to offer an IPO with the ticker: AKUS, if anyone is still following them.

Their AAV platform is promising for genetic hearing loss but they appear to be looking into inner ear cell (hair and possibly support cell via their website) regeneration, too.

 

[FGG]

Live webcast from their conference August 10th:

http://www.globenewswire.com/news-r...at-BTIG-Virtual-Biotechnology-Conference.html

 

[FGG]

Anyone else listen to their webcast?

In the foreseeable future, it looks like they are focused on genetic hearing loss. Of note, the company has apparently invented their own new surgical approach to get their drug into the cochlea uniformly (has to be done surgically with AAV drugs). Though the specifics were confusing because it sounded like he said it was an Oval window approach, then said Round Window but I believe he misspoke the second time and he meant Oval Window because he described moving the stapes footplate in the approach.

It was an interesting talk and I think the company will do well even if it's not directly applicable to most of us in the immediate future. It's obviously good to have more of this research in general, both for the millions who suffer genetic hearing loss, and because the tech may have broader applications. E.g.. The flat epithelia problem of profound long term hearing loss might be improved with something like AAV transduction (which Akouous sounds like they are leaders on) of remaining cell populations (fibroblasts). That's pretty long term though.

 

[Thuan]

Anyone else listen to their webcast?

In the foreseeable future, it looks like they are focused on genetic hearing loss. Of note, the company has apparently invented their own new surgical approach to get their drug into the cochlea uniformly (has to be done surgically with AAV drugs). Though the specifics were confusing because it sounded like he said it was an Oval window approach, then said Round Window but I believe he misspoke the second time and he meant Oval Window because he described moving the stapes footplate in the approach.

It was an interesting talk and I think the company will do well even if it's not directly applicable to most of us in the immediate future. It's obviously good to have more of this research in general, both for the millions who suffer genetic hearing loss, and because the tech may have broader applications. E.g.. The flat epithelia problem of profound long term hearing loss might be improved with something like AAV transduction (which Akouous sounds like they are leaders on) of remaining cell populations (fibroblasts). That's pretty long term though.

I haven't watched the webcast. Forgot about it. But, can you explain why this is a novel approach? Why can't we just use a needle to inject the drug to the round window (without structural compromise of and around the stapes in the oval window) and allow the drug to diffuse naturally in the cochlear medium?

I have always thought that if the drug is effective but the mechanism of delivery is the bottle neck, then there is always a surgical option, albeit quite invasive, to directly inject into the cochlea.

 

[tommyd87]

There

Anyone else listen to their webcast?

In the foreseeable future, it looks like they are focused on genetic hearing loss. Of note, the company has apparently invented their own new surgical approach to get their drug into the cochlea uniformly (has to be done surgically with AAV drugs). Though the specifics were confusing because it sounded like he said it was an Oval window approach, then said Round Window but I believe he misspoke the second time and he meant Oval Window because he described moving the stapes footplate in the approach.

It was an interesting talk and I think the company will do well even if it's not directly applicable to most of us in the immediate future. It's obviously good to have more of this research in general, both for the millions who suffer genetic hearing loss, and because the tech may have broader applications. E.g.. The flat epithelia problem of profound long term hearing loss might be improved with something like AAV transduction (which Akouous sounds like they are leaders on) of remaining cell populations (fibroblasts). That's pretty long term though.

There is a newsletter you can sign up to on their website too which they release each quarter.



The above image is a screenshot of their various planned treatments and their current position.

While obviously they are currently focused on genetic conditions, it is clear that they have made some progress in all aspects that they are looking to treat.

I would be interested in learning whether some of their treatments might overlap and actually treat multiple conditions. Eg whether you could use the autosomal dominant disorder treatment as a substitute for the hair cell treatment or similar.

 

[FGG]

I haven't watched the webcast. Forgot about it. But, can you explain why this is a novel approach? Why can't we just use a needle to inject the drug to the round window (without structural compromise of and around the stapes in the oval window) and allow the drug to diffuse naturally in the cochlear medium?

I have always thought that if the drug is effective but the mechanism of delivery is the bottle neck, then there is always a surgical option, albeit quite invasive, to directly inject into the cochlea.

Briefly, the difference is AAV is a viral vectored therapy and it needs to be directly injected into to its target rather than diffusing in.

 

[wwtsai]

Akouos provided their 3Q 2020 financial results and some updates. Probably the most notable update is:

"Continued progress towards IND filing in 2021 to enable a Phase 1/2 clinical trial for AK-OTOF, a gene therapy intended for the treatment of hearing loss due to mutations in the OTOF gene – Through a targeted delivery of a proprietary ancestral AAV, known as AAVAnc80, containing the OTOF gene, Akouos aims to restore otoferlin expression, potentially restoring physiologic hearing and providing long-lasting benefits to individuals with OTOF-mediated hearing loss. Akouos plans to submit an IND application to the FDA in 2021 to conduct a Phase 1/2 clinical trial. The planned Phase 1/2 clinical trial consists of two parts. The first part is a dose escalation phase designed to assess the safety, tolerability and bioactivity of AK-OTOF, administered to trial participants through a single unilateral intracochlear injection. The second part is a cohort expansion phase designed to assess safety and efficacy."
​

Source: https://investors.akouos.com/news-r...d-quarter-2020-financial-results-and-provides

 

[FGG]

Akouos just released these two presentations:

https://akouos.com/wp-content/uploa...reg-R-Workshop-Presentation_Akouos_FINAL5.pdf

And

https://akouos.com/wp-content/uploa...nference-Michelle-V-Presentation_vFINAL25.pdf

Of note, they discuss their surgical method which I was really curious about. After a surgical approach, they inject directly through the round window and then vent the Stapes through fenestration. Looks interesting and gets their AAV genetic deafness drug through the entire cochlea. They propose that it's safe but would like to see the data (my guess is the Stapes is handled with very slow microdrilling).

 

[wwtsai]

Of note, they discuss their surgical method which I was really curious about. After a surgical approach, they inject directly through the round window and then vent the Stapes through fenestration. Looks interesting and gets their AAV genetic deafness drug through the entire cochlea. They propose that it's safe but would like to see the data (my guess is the Stapes is handled with very slow microdrilling).

Would a method like this possibly remedy the issues other firms like Frequency Therapeutics are having with drug delivery? I know everyone's coming up with their own methods, but all of these firms attend/speak at the same conferences every year. It'd be great to see them bouncing ideas and methods off of each other to improve their own products.

 

[FGG]

Would a method like this possibly remedy the issues other firms like Frequency Therapeutics are having with drug delivery? I know everyone's coming up with their own methods, but all of these firms attend/speak at the same conferences every year. It'd be great to see them bouncing ideas and methods off of each other to improve their own products.

Theoretically, if only a surgical approach would work, this should work imo.

AAV drugs have to be applied directly into the cochlea so they can't use an intratympanic approach for genetic deafness gene therapies.

 

[patorjk]

A bit of news on this company: Last October they were acquired by Eli Lilly, a large pharmaceutical company. It's interesting to see such a large player enter this space. It's also curious why they picked Akouos. Other than the delivery tech discussed here, I don't see what's so compelling - though then again, maybe it's the delivery tech that's going to make all of the difference in the future.

 

[KoolKat]

A bit of news on this company: Last October they were acquired by Eli Lilly, a large pharmaceutical company. It's interesting to see such a large player enter this space. It's also curious why they picked Akouos. Other than the delivery tech discussed here, I don't see what's so compelling - though then again, maybe it's the delivery tech that's going to make all of the difference in the future.

So how many thousands of years until we get the human clinical trial results for this

 

[AfroSnowman]

The New York Times: Gene Therapy Allows an 11-Year-Old Boy to Hear for the First Time

 

[NikoD]

I was just about to post this but you beat me to it.

From Lilly's website:

The first participant to receive AK-OTOF in the study, an 11-year-old at the time of AK-OTOF administration with profound hearing loss from birth, experienced restored hearing within 30 days of AK-OTOF administration. In this individual, hearing was restored across all tested frequencies, achieving thresholds of 65 to 20 dB HL, and within the normal hearing range at some frequencies at the Day 30 visit. Both the surgical administration procedure and the investigational therapy were well tolerated, and no serious adverse events were reported.

"Gene therapy for hearing loss is something physicians and scientists around the world have been working toward for over 20 years," said Professor John Germiller, M.D., Ph.D., attending surgeon and Director of Clinical Research in the Division of Otolaryngology at Children's Hospital of Philadelphia, and a principal investigator of the AK-OTOF-101 Clinical Trial who administered AK-OTOF to this participant. "These initial results show that it may restore hearing better than many thought possible."

In the AK-OTOF-101 trial, eligible participants receive a single, unilateral intracochlear administration of AK-OTOF, with hearing restoration assessed by behavioral audiometry and auditory brainstem response (ABR), a clinically accepted and objective measure of hearing sensitivity. Participants in cohort 1 receive AK-OTOF at a dose of 4.1E11 total vector genomes.

"Children with OTOF-mediated hearing loss are often born with profound hearing loss, yet only a small fraction have undergone genetic testing to receive a definitive diagnosis," said Dr. Oliver Haag, pediatric otolaryngologist, Head of Otolaryngology at Sant Joan de Deu Hospital in Barcelona, and an investigator in Akouos's AK-OTOF-NHS-002 Natural History Study in which the first individual to receive AK-OTOF was participating. "The AK-OTOF-101 Clinical Trial and AK-OTOF-NHS-002 Natural History Study demonstrate the power of international collaboration in the development of new medicines for rare genetic conditions. It is gratifying to see this collaborative effort provide benefit to the first participant to receive AK-OTOF."

Hearing loss is the most common sensory condition, and with no approved pharmacologic treatments to restore hearing, represents a significant area of unmet need in medicine. Millions of individuals worldwide have disabling hearing loss because one of their genes generates an incorrect or incomplete version of a protein the ear requires for hearing. In many of these cases – including for some of the estimated 200,000 individuals worldwide who live with OTOF-mediated hearing loss – delivering a healthy version of the gene to a target cell within the inner ear has the potential to restore auditory function and enable high-acuity physiologic hearing. OTOF-mediated hearing loss is the first monogenic form of hearing loss to be investigated as part of a gene therapy clinical trial.

"We are grateful to the participants, their families, the investigators and other collaborators who are working together with us on this pioneering trial," said Emmanuel Simons, Ph.D., M.B.A., CEO of Akouos and SVP, Gene Therapy at Lilly. "These initial results highlight the potential impact genetic medicines could have on individuals with OTOF-mediated hearing loss and reinforce our mission to make healthy hearing available to all."

AK-OTOF has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the FDA and has received a positive opinion on orphan drug designation by the EMA Committee for Orphan Medicinal Products.

This is potentially the BIGGEST news for hearing research in human history...

I can't contain my excitement! Amazing if true, we might for the first time have a cure for sensorineural hearing loss...

The bit which sticks out to me:

The first participant to receive AK-OTOF in the study, an 11-year-old at the time of AK-OTOF administration with profound hearing loss from birth, experienced restored hearing within 30 days of AK-OTOF administration. In this individual, hearing was restored across all tested frequencies, achieving thresholds of 65 to 20 dB HL, and within the normal hearing range at some frequencies at the Day 30 visit. Both the surgical administration procedure and the investigational therapy were well tolerated, and no serious adverse events were reported.

In the AK-OTOF-101 trial, eligible participants receive a single, unilateral intracochlear administration of AK-OTOF, with hearing restoration assessed by behavioral audiometry and auditory brainstem response (ABR), a clinically accepted and objective measure of hearing sensitivity. Participants in cohort 1 receive AK-OTOF at a dose of 4.1E11 total vector genomes.

 

[Fields]

Very interesting, and heart-warming to read that said child is able to enjoy improved hearing.

Am I correct in understanding that this drug specifically targets a rare genetic disorder that's responsible for a faulty protein?

If so, what would be the impact of this development on other types of hearing loss (ther than than paving the way for further research)?

 

[Koz]

I was just about to post this but you beat me to it.

From Lilly's website:

This is potentially the BIGGEST news for hearing research in human history...

I can't contain my excitement! Amazing if true, we might for the first time have a cure for sensorineural hearing loss...

The bit which sticks out to me:

Massive news for sure. The hope is now they translate this to other forms of sensorineural hearing loss successfully. It's very welcome as things have been so bleak on the hearing loss front since the Frequency Therapeutics shitshow.

 

[Nick47]

This did not restore any hearing. The child was born deaf. The drug addressed the faulty gene that inhibited the development of hearing during the child's development.

 

[NikoD]

Very interesting, and heart-warming to read that said child is able to enjoy improved hearing.

Am I correct in understanding that this drug specifically targets a rare genetic disorder that's responsible for a faulty protein?

If so, what would be the impact of this development on other types of hearing loss (ther than than paving the way for further research)?

They used a viral vector as their delivery mechanism to inner hair cells to change genomic code (gene editing) which restored hearing. The child lacked a specific protein that enables hearing. It was not regeneration of any cells but that's no reason to be disheartened by this.

Breaking this down a bit more:

1) They (potentially) have a working delivery mechanism to inner hair cells (IHC) and there's no reason why repeat treatments won't work. One of the biggest challenges with past hearing trials has been reliable delivery. Important to mention this is gene editing and not drug delivery, though sometimes they try to achieve similar things.

2) If (a pretty big if) a scientist finds a gene which enables regeneration mechanisms, then there's already a working, approved delivery model.

I'm quite sure this is the first time hearing has been restored in anyone and, although this is a very specific disease being treated, it has potential to be adapted to help everyone in our community.

In Akouos's pipeline, there's mention of hair cell regeneration in the early stages. I'm not sure of its current status post the Lilly acquisition but maybe they already have some targets in research and development.

I hope this therapy goes to plan because it'll give pharma companies the confidence to spend money in this area. The wider market for hearing therapy is just huge and waiting to be tapped and Lilly seems to be closer than anyone at this stage.

 

[HighleyTall]

This did not restore any hearing. The child was born deaf. The drug addressed the faulty gene that inhibited the development of hearing during the child's development.

How did you come to this conclusion?

 

[ColinUK]

Didn't Frequency Therapeutics and CNN or someone release a video about how a deaf teacher had their hearing restored after an injection of FX-322 prior to their official trial's failure and stock plummet?

I'm sorry but I just find it impossible to get excited about or to trust anything in this area of research until there is irrefutable proof of something working repeatedly for lots and lots of people.

I mean it's great that other companies are looking at it but the reality is, it's all for nought at this stage in terms of clinical use for patients.