Sensorion’s Quest to Restore, Treat, and Prevent Hearing Loss: Interview with Nawal Ouzren

Hello and welcome to another

episode of this Week in Hearing.

I’m Brian Taylor and our topic

this week is medicine in

audiology that have the

potential to restore, treat,

and prevent hearing loss.

And with us to discuss these

investigational is Nawal Ouzren,

CEO of Sensorion,

a biotech company based

in France. Nawal.

Welcome to this week in Hearing.

It’s great to have you with us.

Hello Brian,

thanks for having me.

Well,

before we dive into this topic

of investigational,

medicines that restore, treat

and prevent hearing loss,

or at least potentially

could do that,

could you tell us a little bit

about your extensive background

in the biotech sector?

All right. Thank you, Brian.

So I joined Sensorion six years

ago
and prior to that my background

was rather actually in a

bigger organization.

So prior to joining Sensorion

I was running the rare genetic

disease division for Shire.

I was actually based in

the US for that role.

And prior to that I was running the

global hemophilia franchise for

Baxter in actually Deerfield

in Illinois.

So I’m a chemical engineer by

background.

I actually started my career in

the chemical industry and then

in the pharma industry

in manufacturing,

quality operations,

process development,

and then I had the opportunity

to become the chief of staff of

the division president

of Baxter Bioscience.

This enabled me actually to move

to the US. From Switzerland,

and it really changed the

trajectory of my career because

it was like an MBA on the job

had the opportunity to learn so

much more about how to run the

business, about the investors,

about actually franchise

strategy.

And it just opened up my horizon

beyond just manufacturing.

Like I said,

that’s a really extensive

background in this space.

So

it’s great to have you on

This Week in Hearing.

Tell us a little bit more about

Sensorion and this is

a really hot topic,

these different types of

investigational medicines.

Maybe we could start with the

mission and vision of Sensorion

as a biotech company. Yeah.

So as you mentioned in your

introductory comments,

we are developing hearing loss

therapeutics and we have

actually three different

pillars.

We would like to treat hearing

loss after it happened,

we would like to prevent hearing

loss in situations where

we know it may happen,

and we would like to restore

hearing with gene therapy for

children who are born deaf.

And we think it’s very important

actually to work in that

therapeutic area of restoring

hearing because.

When you look at the standard of

care for the past 30 years,

it has not changed tremendously.

There were obviously some strong

innovations when cochlear

implants have been introduced,

and it enabled, actually,

people with severe and profound

deafness for children to acquire

the language or for maybe adults

with residual hearing to

continue to be connected

to the world.

But I think it’s the right

moment to transform that and

have therapeutic options,

pharmaceutical options that will

enable people to keep their

natural hearing for longer or to

actually restore hearing for

people who are born deaf.

If you think about the numbers,

obviously the numbers

are tremendous.

The who published a few years

ago, a couple of years ago,

that there are around

466 million people suffering

from hearing loss.

And we expect that number,

unfortunately,

to continue to increase.

That’s really due to

the way we live.

We live in very noisy

environment, and unfortunately,

this just accelerates the

hearing loss for everybody

teenagers, children,

young adults, the elderly.

That’s a very ambitious

vision that you have.

I wanted to ask you

a question about,

and people that are viewing this

can go onto your website and

learn a lot more about some

of the things that you’re

investigating,

but if you could tell us a

little bit more about the drug

that you’ve developed to prevent

and treat sudden hearing loss.

Yeah,

so that’s actually our most

advanced therapeutic.

It is called SENS-401

So that’s the name of the drug.

And as you mentioned,

it has been investigated in a

phase 2 clinical trial.

So it means we treated patients

and we compared them

to a placebo arm.

And sudden sensorineural

hearing loss is actually

a very scary disorder.

People become deaf within 72

hours, and in 60% of the cases,

it is irreversible.

And what we try to do with our

drug is actually to involve the

patients in our clinical

study within 72 hours,

96 hours after the onset

of the sudden deafness.

And we treated them

for one month,

and we looked at the hearing

performance one month after

treatment and three months

after treatment.

And what we have showed is that

three months after treatment,

there was actually a clinically

significant difference compared

to the placebo arm.

And in particular,

for patients who actually

suffered from very

severe deafness.

At the baseline entry of

the clinical study,

50% of them had normal hearing

at the end of the

clinical study.

So that was like day and night

for these patients.

That’s pretty impressive.

You mentioned the phase 2

do clinical trials.

Could you tell us what status

those trials are in right now?

Yeah.

So that was actually the

treatment trial.

After that we wanted to continue

to investigate the potential of

the drug and in particular in

what we call prevention setting.

And currently there are two

phase 2 proof of concept

running in patients.

One is actually in collaboration

with Cochlear.

I don’t know if you’re familiar,

but Cochlear is an Australian

company.

They are the global market

leader for implants.

And the idea here was to develop

a drug device trial focused on

adult patients who have residual

hearing and to see if the drug

would help preserve some of the

residual hearing of the patients

after the surgery.

We have disclosed some

preliminary data actually in

July where we showed that there

is a 20 dB difference

between actually the patients

who were treated with SENS-401,

compared to the patients who

just received the cochlear

implants without the drug.

So these were preliminary,

the study is still ongoing.

We expect actually to release

the data first half

of next year.

So that’s the first clinical

trial in prevention.

The second prevention trial is

actually focused on adult

patients who are suffering from

cancer and who are being treated

with chemotherapy.

And around 60% of these adult

patients who are treated

with chemotherapy,

they will suffer hearing loss at

the end of the chemotherapy

cycle.

So the idea here is to help the

patients who are treated with

chemotherapy with SENS-401

to see if hopefully we can save

these patients and also preserve

their hearing so that they can

live their life to the fullest.

Yeah, that’s really interesting.

And without getting too

technical here,

could you maybe share

a little bit?

And maybe if you want to direct

people to your website

that’s fine.

But could you tell us a little

bit about how the drug you’re

developing helps preserve

hearing after cochlear implant

surgery? Yeah,

so the

ininer ear it’s a beautiful

organ, it’s very small,

very fragile.

We have a very limited number

of sensory hair cells.

We have only 4500 inner hair

cells, 1200 outer hair cells.

So cochlear implants actually

introducing in the inner ear and

then it’s being stimulated

around 20 to 22 distinct

frequencies and this will help

with the hearing outcomes.

So these sensory hair cells,

unfortunately they do

not regenerate.

So once we lose them,

we lose the function.

So you can imagine drilling

during the surgery to introduce

an electrode.

So drilling will cause actually

some maybe noise induced

hearing loss.

Then the introduction of the

electrode will potentially

create.

Some mechanical damage,

probably some inflammation,

probably some death of

the sensory hair cells.

And then once it’s being

stimulated with the current,

probably some fibrosis.

So all of this is very well

known. So SENS-401,

is anti-apoptotic.

What we have shown in our animal

models and in our preclinical

models is that it stops actually

the process of the sensory

hair cell death.

And so that’s the purpose

of SENS-401.

And so that specific biological

mechanism that is being

triggered when you introduce

the electrode,

we can help with the

preservation of some of the

residual hearing.

That’s fantastic. Unbelievable

what is in store for all

of us in the future

Let’s shift gears a little bit

and talk about some of the gene

therapies that you’re

developing.

Tell us a little bit about maybe

a little bit of how they work

and who the target population

for those treatments might be.

Yeah,

I’m going to start with a little

bit of history. So, in 2019,

we thought it was very important

to start thinking about children

who are born with

genetic disorders that will

lead to congenital nerve deafness

And one of the top academic

institutions driving the science

of hearing is Institut Pasteur,

which is actually here

based in France.

So it was very important for me

to get connected to that very

prestigious academic

institution.

First to show them what we were

doing with Sensorion,

but also to get educated on the

work they were doing

on gene therapy.

So all of that ended up in the

structuring of a very important

collaboration between

Institut Pasteur and Sensorion.

And Institut Pasteur,

they were the first one who

identified actually the genes

that were causing deafness,

but they did not stop there.

They started developing some

options for gene therapies.

So we licensed some of their

gene therapies internally and we

are developing them for FDA ind

approval and CTA approval in

Europe and in the UK.

So the first indication that

we started working

is called actually the

restoration of otoferlin.

So there are some babies who

are born because of a DFNB9,

defective gene

and because of that,

they don’t express a very

important protein called

otoferlin in their

inner hair cells.

So it’s like they have a

frozen auditory system,

nothing happens.

So what we do in gene

therapy is like,

you restore the good copy of the

gene and what we have seen in

the animal model is that the

animal starts re-expressing the

otoferlin and it’s

like all after,

then the auditory system

is live again.

It and we see then natural

restoration of hearing across

all frequencies.

So there are around 20,000

children with otoferlin

deficiency in the US and in

Europe it is probably

underestimated, Brian,

because today there is no

systematic genotyping

to identify the gene

causing deafness.

And there are around 1100 new

babies born every single year in

the US and Europe with that

otoferlin deficiency.

So where we are today,

we have filed our clinical trial

application in Europe

and in the UK.

And after that we will

go to the US.

So that’s the first program.

And the second program that

I call the ‘Holy Grail’,

this is actually focused

on the GJB2 gene.

And why I call it the Holy Grail

is because it’s the biggest

cause for congenital deafness in

the world that 50% of the

kids who are born deaf,

it’s because of that defective

GJB2 gene.

What’s very interesting about

that gene also, Brian,

is that beyond the fact that

it’s the cause of 50% of

deafness at birth,

it’s also responsible for two

other types of hearing loss,

progressive hearing loss.

The first one is actually

children losing their hearing

during their childhood,

again because of GJB2.

And the second one,

which was an insight

from Institut Pasteur,

they were partly interested in

actually young adults who start

losing their hearing by the age

of 30 and who become completely

deaf by the age of 50.

And when they genotype them,

compared to the normal

population,

they found a specific GJB2

mutation that was causing this

early onset of presbycusis.

So we are also interested in

actually caring for these

patients because you can imagine

you’re 30, you had your hearing,

you are at the top of your

life at that moment.

You have a career,

you have a family, et cetera,

and all of a sudden you

can’t hear anymore.

It triggers actually some

difficulties that are even

bigger compared to a child

who was born deaf.

That’s really fascinating and

we all look forward to seeing

these kinds of therapies being

used in the clinic in the

not too distant future.

Which brings me to the final

question that I want to ask you,

and that is how do you see some

of these therapies that your

company is creating

that treat,

prevent and restore

hearing loss?

How do you see them standing

side by side with more

traditional therapeutic

approaches in an ENT or an

audiology clinic? Yeah,

it’s a very good question,

actually, because here.

It’s about the future,

like how do we see the future

and the standard of care being

evolved. So I’m going to paint,

I would say,

my best case scenario,

obviously the therapeutic

options.

So let’s focus about the sudden

deafness. So today,

if you look at the patient

journey so for these patients

who are actually losing their

hearing over between

in 72 hours,

what they do most of the time

is that they will go see the

general practitioner and for the

people who are actually

most scared,

they will go immediately to the

emergency room. So here,

as you said,

there are two touching points.

The first one is like the GP.

So in a world where you have an

approved drug that is safe

and efficacious,

hopefully the general

practitioners will be educated

enough to prescribe it or maybe

even to refer to the

ENT in the city,

the local ENT who could

prescribe the drug.

The second option is like the

patients who will end up in the

emergency room and who will see

the ENT at the hospital.

Then at this stage,

the ENT at the hospital

could prescribe it.

So that would be ideally for me,

first line treatment.

Obviously, if it doesn’t work,

if some patients are

non responders,

then it could be the traditional

pathway,

maybe explore hearing aids,

depending on the severity.

And for really the ones who are

more severe than cochlear

implant,

if you think about

the prevention.

So the patients with cochlear

implants will receive a cochlear

implant or the patients with

the Cisplatin treatment.

So let’s first focus on

the cochlear implants.

So in this case,

the patient is received by an

audiologist or ENT surgeon who

will speak about the different

options. And obviously,

if the doctor and the patient

think that cochlear implants

is a good option,

if the drug is being approved

and being safe,

I can see a world where they

would prescribe to the patient

to take that drug one week

before the cochlear implant

surgery and then follow

up for one month,

two months,

depending on the clinical study.

Right. So for me,

that would become standard

of care.

If you preserve the residual

hearing, the drug is being safe.

For me,

that would be concomitant

patients who suffer from cancer.

The other case is that

the oncologists,

when they working with their

cross functional team,

so they have ENT surgeons,

obviously, et cetera,

as part of the protocol.

They would also prescribe

SENS-401 again to be prescribed

throughout the chemotherapy

cycle to preserve the hearing.

So that’s for the drug and

then for gene therapy,

obviously in this case,

the patient journey.

So there are newborn

screening in

and then we will see if the

baby is born having actual

hearing loss issues.

If there is hearing loss issues,

then what we would recommend,

and it’s not done in

every country,

is to immediately genotype

the child.

And if the child is actually

identified with one of the

genetic mutation where gene

therapy could be an option,

then there will be a

conversation between the doctor

and the parents about the

therapeutic options.

One option is gene therapy,

the other option is

cochlear implant.

The challenge is that if the

parents choose cochlear implants,

you can’t treat the child

afterwards with gene therapy.

Because of the challenges

I mentioned,

the fibrosis, the apoptosis,

the introduction of

the electrode,

but the other way around

is possible.

You could start with gene

therapy and if it doesn’t work,

you can still have cochlear

implant as down the road, right?

Yeah, exactly.

That’s a lot for our listeners

and our viewers to think about.

Very exciting times.

I’m with Nawal Ouzren,

CEO of Sensorion. Nawal,

If people want to learn more

about your company,

some of the studies that you’ve

been undertaking,

how can they learn more?

Yeah,

so there are a lot of resources

on our website, Sensorion.com,

as you said,

there are actually a lot of

material where we’re showing

some of the data,

where we have actually

interviews from doctors,

independent doctors,

where they can see the sites,

the different clinical sites

where we are working.

If people are curious,

we are also very open to receive

emails and we can refer them

to KOLs. We know in the US,

in Canada, whatever the country,

if parents are actually

exploring their options and

they’re looking for different

type of information,

patient advocacy group,

as I said,

different ENT centers of

excellence across the

different countries.

But the best way to start is

either to go on the website and

we have actually a

contact folder.

So people can contact us or they

can send us an email directly.

We receive actually every week,

almost like emails from

different patients who are

looking for resources.

I can imagine, that’s great.

Well,

thanks again for your time.

We really appreciate it and we

look forward to maybe having you

on our broadcast down the road

after you’ve gotten a few more

clinical trials under your belt.

Well, I’m really grateful Brian,

for the opportunity.

And have a good day everyone.