Pioneering Drug Development for Hearing Loss with Dr. Jonathan Kil of Sound Pharmaceuticals

In the future,

drug based therapies will offer

a treatment solution to

individuals with hearing loss.

Sound Pharmaceuticals, Inc.

Is a privately held biotech

company currently developing

therapeutics that will

enable doctors and patients

with solutions to.

Prevent and treat various forms

of hearing loss. Today,

I’m joined by doctor

Jonathan Kil.

He is the CEO and CMO at

Sound Pharmaceuticals.

Welcome to the show.

Thank you so much for your time.

And if we could start

out Jonathan,

by talking about your background

and your company, please.

Yes, well,

thank you for that introduction.

So when I co founded Sound

Pharmaceuticals.

As an MD, PhD that trained in

auditory neuroscience

and otolaryngology,

I was somewhat

frustrated by the lack of

options we could offer patients.

So the goal has been since the

beginning, now 22 years ago,

to develop

the first drug that could

treat sensorineural

hearing loss and

potentially tinnitus.

Tinnitus is often a comorbidity

with hearing loss,

and probably about

50% of patients.

Who complain about their hearing

loss also complain

about tinnitus.

So as a student,

I was critically

aware of one of the major themes

of the origins of

sensorineural hearing loss,

and that was a loss

of auditory hair cells.

So I had studied ways of trying

to regenerate them,

and that’s still a

work in progress.

Then,

because I wanted to enter

clinic faster,

I thought of a non regenerative

approach,

a small molecule that

we thought

could be very helpful

in acute acquired

forms of sensorineural hearing

loss and tinnitus.

And for this reason,

we first focused on acute noise.

So in this case, you know,

when the injuries come.

And in laboratory experiments

with animals, we

do noise induced hearing

loss experiments.

And oftentimes we give the

animal an otoprotective drug

before, during and after the

noise

and then follow the animal

for potentially months.

And the idea there

is to prevent

noise induced hearing loss,

maybe treat it.

And we were very successful in

our small molecule approach.

It’s a novel chemistry,

a new chemical entity,

a drug that’s never been

approved before.

And we have now launched that

Through 13 different studies,

we’ve completed nine.

We’re wrapping up four.

We now have our 6th

Investigational New

Drug application, an IND

as it’s called,

is required for a drug that’s

never been approved,

or an approved drug going into

a different indication.

Five of six of our indications

focus on different forms of

hearing loss and tinnitus.

Our most advanced clinical trial

is a pivotal phase three

and Meniere’s disease,

which involves hearing loss,

tinnitus, vertigo or dizziness,

and that disease is not

necessarily considered acute.

Again, noise.

We know when the insults coming.

One of our other IND’s involves

aminoglycoside ototoxicity.

We’re working with the cystic

fibrosis foundation on that.

And there we know when the

patient’s going to get the

IV aminoglycoside.

And we have positive phase

two results there,

as we do an acute noise.

But our most robust program has

been in Meniere’s disease.

So we’ve already completed

two studies,

we’re completing a third.

And what we’ve been able to do

there is improve their hearing

and their speech discrimination,

as well as their tinnitus

from baseline.

So these patients

are preventing,

with an acute exacerbation,

they’re active.

The problem with Meniere’s

disease is not only is it four

different components,

but it’s often episodic.

You can have good months

followed by bad months,

good years followed

by bad years.

And so we’ve enrolled a wide

range of patients some as young

as early thirties to

mid seventies.

And I’m amazed how well our drug

has done to improve low

frequency hearing loss,

speech discrimination

and tinnitus.

In the study population,

that averages about 55 years.

So we studied young adults

exposed to acute noise that

resulted in an eleven page

primary research publication

in The Lancet.

So dare

I call it groundbreaking,

but it was groundbreaking

for several reasons.

That involved a very short

duration of treatment,

because their exposure to loud

sounds was very short. So,

essentially,

ebselen given before,

during and after,

prevented the noise induced

temporary loss of hearing.

So, again,

these study participants had

good hearing to start off with

with our ototoxicity work in the

cystic fibrosis foundation

population. These patients,

although relatively young,

about 30 years of age,

already have the hearing

of a 50 year old.

And that’s because they’ve

received so many ototoxic

medications in their lifetime.

And then the meniere’s

pop is 55-75,

and they’re on a lot of

different medications.

So the great thing about our

drug is it can be given orally.

It appears to be very.

Well tolerated or safe.

And we haven’t identified

any dose-limiting drug,

drug interactions. Today,

across all our different

studies,

we’ve enrolled over 850 people,

and by the end of next year,

it’ll be over 1200.

So right now,

we’re finishing the pivotal

phase three Meniere’s study.

We’re opening an expanded access

program to further test that for

six and twelve month durations.

We are collaborating with a

cochlear implant company now to

test our drug given before,

during and after a

cochlear implant.

And this is to preserve

residual hearing.

There are many adult candidates.

They qualify for cochlear

implant because of their poor

high frequency and mid

frequency hearing,

with poor speech

discrimination,

but they still have aidable

low frequency hearing.

One of the consequences of

cochlear implantation,

and this is described

to the patient,

is you may lose that

residual hearing,

and now you may no longer be

able to use your hearing aids.

In addition, if that happens,

you can’t use the hybrid system,

which involves electroacoustic

stimulation.

So this is an issue.

Many patients do not want to

lose whatever aidable,

low frequency hearing that they

have that’s critical for music

appreciation and some

speech sounds.

So we’re

in a very interesting way,

going from acute to

chronic disease,

subdividing phase two

study populations,

developing protocols that we

think can really hone in

on not only an outcome,

but an endpoint that the FDA

will recognize as being

clinically relevant. So today,

no one has received FDA approval

for a drug to treat sensory

neural hearing loss,

or tinnitus.

We manage people with

these diseases,

mostly with hearing aids,

and then if you become deaf,

cochlear implants on

the tinnitus side,

we try masking,

or we tell the patient

to try masking.

Its unclear whether we know

enough about tinnitus for

a drug to be effective,

and that’s what’s so surprising

about our effects in

Meniere’s disease.

Here’s a patient with

a chronic disease

oftentimes in the aging period.

And most people would think that

a drug to treat tinnitus in the

years would have to focus

on the brain.

Many people believe after five

to ten years of tinnitus,

there’s been these plastic

changes in the brain,

this maladaptive

neuroplasticity.

So you hear sounds in the

absence of sounds,

I believe it’s probably mix both

peripheral and central.

And

our drug seems to

work well there

It’s actually exceeded our

expectations on how

well it’s worked.

We thought it would

be very safe,

and we wanted a safe oral drug.

We knew there are limitations

to certain classes of drugs,

especially drug -drug

interactions and repeated

injections across the eardrum.

That will be difficult,

especially as the patient ages.

There have been well documented

cases where placing

corticosteroids across the

eardrum can impair wound healing

in the eardrum and set you up,

potentially,

for an otitis media.

We’ve actually seen some of

those patients who are on other

drug trials come into our

trial after a washout.

So, as you mentioned,

we’re still privately held.

To date,

we’ve raised about $65 million

in equity and grant funding.

We’ve been funded by the

Department of Defense for our

hair cell regeneration work.

We’ve been funded by the NIH.

And

these last two years have

actually been our

best two years,

even with the pandemic that

heavily impacted the enrollment

on our cystic fibrosis

ototoxicity study.

But after seven years of

completing a three part phase,

one, two,

the data are very supportive.

They’re positive.

So we’re advancing,

and that’s good to see.

Aminoglycoside ototoxicity is

not only a major issue in

patients with cystic fibrosis,

but other patients that require

IV and inhaled aminoglycosides.

So patients with bronchiectasis,

they’re at incredible risk for

recurrent bacterial infections.

There are patients out there

with a atypical type of

tuberculosis called non

tuberculosis mycobacterium.

They have a very,

very hard time trying to take IV

amikacin for months because

these microbes are very

slow growing.

You can’t kill them like

simple bacteria.

With two weeks of treatment,

they require at least two

months of treatment.

I’ve seen some protocols where

it’s six months of treatment.

You can’t take six months of an

aminoglycoside and not have

hearing loss, tinnitus,

dizziness. In fact,

many of the pulmonology

infectious disease doctors that

we work with, when I ask them,

an NTM patient comes in,

they’re exacerbating, well,

we start them on IV amikacin

for four to eight weeks,

and then we transition them

to inhaled. I go, why?

They complain of being dizzy and

having tinnitus. So, you know,

we’re going to do a chronic

study in that study population

and start that enrollment at the

end of the year. So this is,

in some respects,

not what I imagined for myself.

I imagine myself being an

academic otolaryngologist

doing research.

But I had trained in some

of the more prominent

labs involved in hair

cell regeneration.

And after doing that,

I realized they were never

going to develop a drug.

It was just,

it was not going to be

a way to develop a drug.

And quite frankly,

that’s probably not the role for

academia. It’s more discovery,

maybe some early translational

work,

but people don’t have funding

nor the commitment to do all the

IND enabling work get

through a phase two

clinical trial.

So if you go from idea to

hopefully a phase two result,

that took us

over ten years. Wow,

14 years to be exact.

We could have been faster,

but it was difficult to get the

right study population with the

right controls within active

duty military,

we know it’s a big issue,

but getting that quiet

period before noise,

having a regimented noise

exposure with or without hearing

protected devices,

and then the quiet period

because you need to follow them

up for at least a week,

potentially one month,

to see the resolution of the

temporary threshold shift or the

evolution of the permanent

threshold shift.

So there are a lot of

difficulties dealing with

patients with hearing

loss and tinnitus,

not just the measurements,

but how will you define

baseline?

How will you define a clinically

relevant endpoint?

So there are a lot of things

that need to align for

successful drug development.

And quite frankly,

we have been successful where

many others haven’t.

When we started in 2002,

we were it.

Then we saw companies

start in 20 03,

2005, 2008, 2012 and so on.

We’ve seen ten companies

come and go since then.

Five went public and they’re

no longer public.

Only one was acquired and

I think has successfully

translated a gene therapy

to a phase one. Two,

all the others failed.

And five of those companies

were private.

And essentially they either

closed or repositioned

themselves to go after other

diseases like multiple

sclerosis or seizure.

So

it’s been a long haul

and after 20 years,

I understand why there are no

drugs for hearing loss

or tinnitus.

It’s been a very humbling

journey,

but it’s been a very fruitful

journey. We now get emails,

notes conveyed to us by

clinicians about patients who

have been on our studies,

who saw benefit.

Then after they went

off our study,

have seen a return to symptoms

and want to get back on a study.

So we hope that the end of

next year that the FDA

Could review and approve the

first product, our product,

SPI 1005 ebselen,

for the treatment of sensorineural

hearing loss and tinnitus.

It’ll probably be in a meniere’s

indication. First,

and then we’ll have multiple.

Other indications that

we test our drug in.

We now know it’s safe enough

to dose for six months.

It may be safe enough to

dose for twelve months.

We don’t know that yet, but we.

Have confidence with six months

of treatment. Now,

this potentially opens us up to.

All the chronic diseases or

chronic indications we didn’t

want to go after as

a young company.

So age related hearing loss,

chronic noise.

Induced hearing loss,

and maybe chronic tinnitus.

So we’re very excited

about that.

Next year will be even better

than these last two years,

I think.

Well I’ve been a fan from afar.

I’ve watched your growth

over time,

and as we look at the industry

and. The marketplace,

you’re right.

There have been folks that have

entered and then exited

in this space,

I will share with the audience.

You have a very nice

website that.

Offers a pipeline of where

your products. Are,

and we’ll certainly direct

Individuals who are interested

to that so.

They can see you know,

what you’re studying and where

you’re at in terms of those

testing protocols and phases

and what have you.

The one question that

I do have for you,

based on the commentary that

you’ve shared, is,

and I’m speaking perhaps on

behalf of clinicians

and practitioners,

what.

Do you see the role of the

typical audiologist for someone?

Let’s use the meniere’s

as an example.

For someone who walks

in with meniere’s.

Into a physician’s office.

What’s that journey going

to look like with your

pharmaceutical product?

Yeah,

that’s a very good question.

It’s a very

complex issue.

So when patients are ruled

in for meniere’s,

it’s typically by an

otolaryngologist.

They will typically work with or

have on staff an audiologist

that will confirm the

definite diagnosis.

So the definite diagnosis

requires audiometric

documentation.

Of low frequency hearing loss.

So an audiologist is

critical there,

and.

If the vertigo is severe enough,

they may consider

more ablative therapies.

So everyone is typically put on

a low salt diet. Thiazide,

diuretic.

Some patients get beta histine

from Asia or Europe.

They’ll try an oral course

of steroids.

They’ll try locally

injected steroids.

Some have even historically

received intratympanic

Gentamicin to lesion those

overactive vestibular

hair cells.

We don’t know why

the vertigo.

Within two to five years seems

to burn out or be less severe

or lengthy in duration.

That doesn’t mean you can’t have

recurrent episodes years later,

but they tend to be less

intense, shorter in duration.

A small proportion will evolve

to surgery and the lymphatic

sac, deconversion,

with or without a shunt,

even a labyrinthectomy or

nerectomy. But thankfully,

that’s only 5% of patients.

As the patients age,

they complain more about hearing

loss on one side,

some patients have gone deaf and

received a cochlear implant,

the chronic tinnitus.

This is a big feature in our

older patients, 65 and older.

They’re still active,

some of them still working,

and it becomes difficult for

them to communicate in a

complex, noisy environment.

They’ll try hearing aids.

So audiologists are critical

for fitting hearing aids.

They’ll try masking,

and audiologists are critical

for tinnitus retraining therapy.

And then the audiologist will

manage their chronic conditions.

Once they have decided, no,

I’m not going to go into

surgery. I’ve tried steroids,

systemic and local.

While they do see an ENT hoping

for something new,

there really hasn’t been much

to offer them other than,

let’s try and medically manage

you for at least the

first six months,

see if severe vertigo is such

an issue that we consider

a surgery.

So we’ve seen all these types of

patients on their journey,

if you will,

and what we hope to offer is the

first medical solution

or treatment

to become almost the standard

of care with low salt diet,

thiazide, diuretic,

and the

American Academy of

Otolaryngology did a meta

analysis and published in 2020

as part of their updated

guidelines for clinical practice

of Meniere’s disease and

the medical management.

The data were rather weak.

You know they aren’t

FDA approved.

Even intra tympanic

dexamethasone is not FDA

approved. ENTs do it.

They think it could relieve

the episodic vertigo.

But we had a lot of patients

where they were becoming

steroid refractive

We saw a lot of them and they

came on our trial and they

benefited, which was surprising.

I thought if our drug

was going to work,

it was going to work in the

first year of long uses.

I didn’t think it would work in

people who had a 10-20 year

history of Meniere’s disease.

Unfortunately,

two thirds of Meniere’s

disease is unilateral,

and we don’t know why.

So one ear is affected,

but five to ten years later,

a proportion will develop

Meniere’s in the other year,

and that’s really discouraging

for the patient,

so we get calls and

emails every day.

When is your drug going

to be approved?

When can I get on expanded

access? And,

you know,

we are about to open up our

first expanded access program

in the US at probably four to

six centers that enrolled

our pivotal phase.

Pivotal phase three,

Meniere’s trial.

So the audiologists and ENTs

there are skilled at prescribing

it and doing all the assessments

we want.

So

who knows? Maybe one day,

audiologists will have

prescribing power for

some medications.

Especially if you have a

doctor in audiology.

I don’t know why you wouldn’t be

allowed to prescribe certain

medications that are

considered safe.

A thiazide diuretic can be safe.

Many patients have a

prescription of meclizine

antivert for their nausea and

vomiting associated with

dizziness. So,

yeah, we’re very hopeful.

Well,

and as you’re talking about this

progression and this expansion

into understanding the hair

cells and these different

limitations and manifestations

that patients experience,

and as you pointed out,

we don’t have prescribing

rights yet.

The hope is that as we grow

as a doctoring profession,

that we then will also have the

opportunities to participate

more particularly given

workforce shortages,

both on the medical side and

on the allied health side.

And as the population continues

to trajectory in the

upward direction,

there’s gonna be more and more

need. Having said that,

have you guys had any

discussions about potentially

AI participation in this,

how that might play out in some

of your conversation?

And this may be very premature

or whether or not the patient,

he or herself should be

monitoring themselves using

online screenings or some sort

of a online mechanism.

I think it’s too early for AI

because of the black box

that is hearing loss.

I do think some of the online

and app features that I’ve seen

have certainly gotten better at

screening for hearing loss.

There is a company called

Shoebox that is developing a

tablet based audiometer,

but it’s really for screening,

not for diagnostics,

at least not yet.

But as the components of you

know, personal computing,

phones become better

and more reliable.

I could see people doing a

lot of self diagnostics,

and I do know people who have

done this for the last five

years, especially with PSAPs.

And now, quote unquote Over the

Counter hearing aids after the

FDA Rule was codified in 2022.

So there are people, I think,

who can benefit from that,

whether that really gives them

the type of hearing they want in

a complex, noisy environment.

This is still a limitation

of external. Devices,

and we see this all the time.

My youngest son is actually

hearing impaired.

So at the age of five,

he was fully diagnosed with

bilateral mild to

Moderate sensorineural

hearing loss.

So if you didn’t know

any better,

you’d say he has the audiogram

of a 50 year old.

So he’s had hearing aids and

speech oral for the last eight

years. And thankfully,

his hearing loss is stable.

So at four, six, and 8 khz,

he’s between 40 to 55 decibels

of hearing loss,

bilateral and symmetric.

And his words in quiet test

scores are, you know, 100%.

But when they’re noisy

environments, background noise,

he struggles.

If he’s trying to say

something to.

Me from the back of

the car

and hear what I’m saying,

you know,

in the front of the car,

he has to ask me to repeat it

because we kind of forget

how much we rely on

facial cues. So oftentimes,

as I get older and.

Approached by a friend,

typically their spouse,

he needs to see you.

I go, well,

I’m not a practicing ENT.

I’m not a practicing

audiologist.

I can refer you to some

outstanding people in Seattle.

He’s in this state of denial

about his hearing loss.

And then as we’re talking,

I said. He goes, you know,

I can hear you. Well, you know,

I’m getting what you’re saying.

I go, yeah,

but if you don’t see

my mouth move,

and he

back and go, like,

you know, and so.

Many people have said they

finally decided to get a hearing

test. 38, 39, 42.

They found themselves physically

compensating for their

hearing loss.

They put their better ear

towards the speaker.

Physically or in person.

They made sure they faced the

person and their lips.

And when they catch themselves

doing that.

They realize,

I have a hearing problem.

Okay, but, you know,

and you guys.

Are experts on the market

metrics of this.

I think the data are still

the same. Right?

Ten years from where

someone saw their

first audiologist to where they

got fitted for a hearing aid.

And that amazes me.

Ten years, you know,

I thought completely.

In the canal hearing aids

would change that,

but

really hasn’t at least the.

Last data I saw.

Yeah,

and it’s between seven and ten

years. You’re absolutely right.

And it is the.

That is the.

The linchpin that audiologists

and the industry.

Has been trying to solve,

the OTCs hopefully will

assist in that.

The OTCs are still

in their infancy.

And we’ll see down the road

where all that takes us.

But I think it’s an

exciting time.

The products and the treatments

that. You all are working on,

I think.

Are absolutely tremendous

and very much needed.

But basically

the areas in which you all are

targeting these issues,

whether it’s otoprotection,

the chemical protection and

the regeneration areas,

is essential to our future.

And I’m really,

really excited to.

When your product is

FDA approved and.

It actually hits the

market and allows.

Individuals that opportunity

to improve their quality

of life so that they can spend

time with family and friends.

If they’re employed,

they can continue

to be gainfully employed and do

The things that they need to do.

Very much looking forward

to that. Do you,

have you said next year is

the timeline for that?

Did I get that right?

You’re hoping for

that next year?

Yes.

If this pivotal phase three

reads out the data we

hope it reads out,

we’ll begin the new drug

application process next year.

There’s some additional non

clinical work we still have to

do to get this drug approved for

first use and then potentially

chronic use.

So it’s still a work

in progress,

but we have so much positive

data behind this.

We’ve built a good base.

We have six INDs now,

five involving hearing loss

and tinnitus indications.

I think we’ll have three

more next year.

Based on these chronic

indications.

We want to go after that

are slower evolving.

Age related hearing loss doesn’t

usually result in a ten to 20

decibel loss of hearing at

one tested frequency.

That can happen with noise,

ototoxic drugs many years.

So we’ll have to treat people

probably for at least six to

twelve months to see an

appropriate separation between

placebo and active that’s

clinically relevant and

statistically significant.

But

given the robust response we’ve

had from patients who

completed the study,

been off study for

a month or two,

and now sending us emails saying

my symptoms have returned.

One of the things that as

clinicians we have monitored and

talked about is just the fatigue

associated with straining

to hear.

And that has been documented

in single sided deafness.

Now that has been documented

in pediatric children.

Is your child exhausted when

they come back from

the day of school?

We’ve talked with some patients.

And they have decent hearing

on one side,

poor hearing on the other.

But when they go to a scientific

conference, a lot of noise,

a lot of voices,

they’re exhausted.

They say after 6 hours

straining to hear.

So fatigue has become a very

interesting quality of life

issue that we didn’t think

about ten years ago.

Yeah.

Yeah.

So,

any last words,

thoughts that you want to

share with the audience?

Well,

it’s taken 20 years to

get to this point

but I think we’re within two

years of getting the first drug

for hearing loss and

tinnitus approved.

And that will be a paradigm

shift in our field.

Hopefully it’ll be the first of

many. We have many ideas.

As I explained to the

pharmaceutical industry

when I asked other CEO’s

of bigger companies

what they think the top 20

chronic diseases are,

we rarely hear hearing loss,

tinnitus and dizziness,

and they’re shocked when

I tell them, well,

sensorineural hearing loss is

no worse than three

to five tinnitus,

probably nine to twelve.

Dizziness is now getting

recognized.

That’s probably somewhere

between 15 to 18.

So those are three diseases of

the inner ear that impact tens

of millions of Americans,

which we don’t have a single

therapeutic drug.

So hopefully we’ll change that.

So I want to thank

your audience.

I get a lot of complimentary

emails LinkedIn messages.

People are happy that we’re

working on this and hopefully

in two years we can have a

different conversation,

maybe even in one year as

we start the process,

and then in two years complete

the process.

Well,

we look forward to

your successes,

we look forward to

recommunicating with

you down the road.

And once this FDA approval

comes through and

as you pointed out,

it’s a paradigm shift.

And the profession,

at least in audiology and I’m

sure in otolaryngology as well

needs this as it continues to

better serve those individuals

who have hearing loss that

continues to trend upwards and

affect millions and millions

of individuals.

That’s good.

Well,

thank you again for this

time and attention.

Thank you for reaching out and

it’s a pleasure to meet you.

That’s my pleasure too.

Thank you.