Trends in Auditory Regenerative Medicine: Spiral Therapeutics Novel Drug Delivery System

Brian Taylor: Hello, and welcome
to another episode of This Week

in hearing, I’m Brian Taylor. My
guest today are Hugo Peris who’s

the CEO of Spiral Therapeutics.
And with him today is their

chief medical officer, Dr.
Charles Limb. And they’re here

today to make us a little
smarter on the topic of auditory

regenerative medicine, and some
of the important work that their

company is doing in this area.
And before I start asking them

some questions, and having them
they’ll tell us about their,

their studies and their
projects. I’d like them to maybe

start by telling our audience a
little bit about themselves and

about their company Spiral
Therapeutics. So Hugo, I’ll go

ahead and start with you.

Hugo Peris: Thank you, Brian.
And thank you for having us

today. It’s a pleasure to talk
to you. So Spiral started in

2016. As a hearing company,
we’ve been working for the last

seven years on advancing our
pipeline of hearing

therapeutics. And we’re
currently focused on developing

a treatment for many years
disease, which is already in the

clinic.

Brian Taylor: Great. And Dr.
Limb, you’re the chief medical

officer, can you tell us a
little bit about your background

and what you do at spiral
therapeutics?

Charles Limb: Absolutely. And
thanks, Brian, for having us. So

I’m a neuro otologist. I’m
currently the Francis A. Sooy

Professor and chief of otology
neurotology. Skull base surgery

at University of California, San
Francisco. And when I moved to

UCSF it was after being at Johns
Hopkins Hospital for almost 20

years. And one of the great
things about moving to UCSF was

the opportunity to collaborate
with some of the advances in

industry. And so, Hugo had
approached me by now about six,

six and a half years ago to just
learn more about Spiral. And

that was at a point where I was
feeling some frustration with

what was available to us in our
standard clinical approaches to

hearing loss. And so I found
just great excitement and energy

in the idea of looking outside
the box and just sort of like

thinking about alternate ways to
get what our patients need. And

so with that kind of motivation,
I joined spiral as the Chief

Medical Officer where I still
continue to to treat patients

surgically at UCSF, but with
spiral have been working with

Hugo in the team to try to
advance these really important

developments in treating
Menieres disease and other

neurologic disorders.

Brian Taylor: I think that’s a
good a good springboard into the

My first question for you, I’ll
direct this to Dr. Lim. And that

is, and I think, I mean, this is
based on my own experience as an

audiologist working in ENT
practices years ago, and also

what I saw on your website, and
that is that something like 90%

of inner ear disorders are neuro
degenerative or inflammatory in

origin. So maybe you could give
us some examples for our

audience of of these types of
conditions that are commonly

seen in an ENT practice. And
then, as a follow up question

that give us maybe a little idea
historically of why those kinds

of conditions are so challenging
to treat.

Charles Limb: Yeah, so you know,
let’s be perfectly clear about

one thing, there’s no FDA
approved medications to treat

hearing loss today. If you think
about where we are in modern

medicine, and the fact that we
have the ability to restore

hearing with cochlear implants,
in somebody who’s deaf, the fact

that we don’t have a single
medication that can target

hearing loss is really kind of
astonishing. Also, if you are a

clinician, you realize very soon
that we don’t have a whole lot

to offer besides steroids. And
the unusual thing is that if you

list kind of a differential
diagnosis broadly of different

hearing loss conditions, whether
it’s sudden sensorineural,

hearing loss, Meniere’s disease,
noise induced hearing loss,

chemotherapeutic, ototoxicity,
and so forth, if you just kind

of go through all of the very
common ear disorders that lead

to hearing loss, you’ll find
that we treat all of those with

steroids. And the reason for
that is not that steroids are,

are used so perfectly in those
settings and indications it’s

that we don’t have anything else
that seems better right now. And

the linkage between those
conditions appears to be some

degree of neuro inflammation, or
cochlear inflammation that seems

to benefit from the anti
inflammatory effects of

steroids. And so the limitation
is partly in that we need more

specificity and not just one
medicine for all conditions, but

also that steroids are very,
very effective. You know,

they’re it’s an impressive
medication, but we need to be

able to use it better. And so a
lot of what we’ve been thinking

about that Spiral is how to get
something more effectively,

where it needs to get to so that
whatever the medicine, whether

it’s a steroid or something else
it can do its job better.

Brian Taylor: So maybe that
would be my next question would

be How does Spiral Therapeutics
attempt to solve some of the

problems that you just
mentioned?

Hugo Peris: Thanks, Brian. I’ll
take this one. So at spiral

we’ve been focusing on looking
at the space it’s been great

learning from a lot of the
companies that have been trying

to address this problems of the
inner ear and trying to advance

drugs. For a range of
indications, it’s been

interesting to us to see some of
the reasons why some of these

attempts have failed that
progressing towards the clinic

and towards approval. And we’ve
been trying to learn about this,

this failures and trying to
apply a different approach to

developing our treatments. The
first thing that we’ve looked

at, and one thing that we’re
very focused on is drug

delivery, we think drug delivery
is one of the biggest challenges

of access and of treating inner
ear disorders, systemic drugs,

or drugs supplied systemically
don’t reach the inner ear at

effective concentrations, for
the most part, because the

cochlea is beyond the blood
brain barrier. And we also know

that local delivery, the way
it’s been traditionally done

with blind intratympanic,
injections might not be the best

solution for effective and
reliable deployment of drug

treatments. So we’ve been
thinking about that. And we’ve

been building a drug delivery
platform, which allow us to

deploy drugs to the inner ear
more precisely, because we do

that still minimally invasively
and locally, but under

regionalization. And that day,
gives us the opportunity to

place drug delivery systems that
will last longer. And that will

be precisely placed so that we
can have that that effectiveness

of a treatment across every
patient that we treat in

clinical trials, and hopefully
beyond. So that’s been the core

of our technology and the focus
that we’ve been putting on in

developing our platform, then
once we build that, we’ve taken

this step of advancing treatment
for many years, and that’s a

steroid treatment that we
already have in the clinic, like

I explained before, this
treatment, we hope will help us

validate our platform, our drug
delivery platform, and we’re

also trying to take those
learnings from things that have

happened before in the field
from all the experience that has

been accumulated by companies,
and obviously all the physicians

that have been using steroids
for many, many years, a lot of

literature that has been
published about this, and trying

to make some changes, think
about what are the really

clinically meaningful outcomes
for for patients, in either

defying those, those results,
and making sure that we are

demonstrating that effect versus
a placebo treatment. So that’s

been the focus of the work. And
beyond that we’re going to

continue to advance a pipeline,
think about other indications in

you know, mostly related about
in hearing and neurodegeneration

of of the inner ear.

Brian Taylor: Well, that brings
me to the next question, which

is about the the recent
announcement about you’re

receiving funding for a phase
two trial of SPT2101. I hope I

have that. Right. Could you tell
us a little bit about that

trial? What’s the objective of
the trial? What are you trying

to achieve, and maybe a little
bit about the design of the

trial?

Charles Limb: Sure, maybe I can
take that one. So as Hugo

mentioned, SPT 2101, is a sort
of special steroid formulation

that we have, which we’re
delivering to the inner ear at

the round window. Under direct
visualization, using minimally

invasive approaches, we’ve
completed an initial phase one

study in Australia, and that
study was was quite promising.

And our goals with the phase two
study are to build upon what we

learned in phase one. And in
specific, we want to get the

technology in the hands of more
providers. And you know, anytime

you’re developing something like
this, it’s you’ve kind of come

up with the idea. And you’ve
sort of established a proof of

principle and proof of concept.
But now you have to actually see

how scale how scalable it is to
other practitioners. And so we

would like more otologists, to
now be involved. And so with

that goal in mind, we’re
launching a multicenter trial in

Australia, which just has just
begun in four sites in

Australia. The initial results
from the phase one study will be

published, published and
presented at the upcoming Asia

Pacific otolaryngology meeting
by one of our colleagues, Dr.

Jeffery Cooper thean. But the
phase two study will involve

more otologist that can be doing
this and with the goal of

refining our, our surgical and
in clinic procedural approaches,

but then also establishing
effect size parameters, you

know, we have a clear sense that
this treatment is effective. And

now we have to increase the
sample size and really learn

what the effect sizes are and
how they relate to our placebo

arms.

Brian Taylor: Is it I want to
make sure that I have this

right. The treatment is for
people that have been diagnosed

with Menieres disease, right?

Charles Limb: Correct. And so
what we’re doing is we’re

enrolling two patients with
active disease. You have to

basically be dizzy currently
with Menieres disease and we’re

looking at basically vertigo as
the primary endpoint vertical

control for Under these
conditions, were using a one

month run in period where the
patients have to report a

certain level of dizziness in
order to have the treatment so

that we can see if the treatment
helps them. And, you know, we’re

excited. You know, I would say
this, this is something that

we’ve, clinically people have
used steroids exactly for this

purpose for a long time, but the
outcomes have always been

variable. You know, there’s some
patients that seems to work

great for and others that it
doesn’t. And so what we’re

really trying to figure out is
how do we improve upon that so

that the steroids can really how
we can take advantage of the

full anti inflammatory power of
a steroid by putting it where it

needs to be placed in the ear
and knowing that it’s there for

that one particular patient.

Brian Taylor: yeah it’s really
great. I hope that the results

are favorable.

Charles Limb: As to we, ya no,
it’s exciting. And we, you know,

like the field needs something
and we are we’re actively

pursuing this with great, great
hopes and great ambition.

Brian Taylor: That’s great. Are
there any other drugs in the

pipeline that you plan to
develop for treatment of

interior disorders or any other
type of otologic conditions?

Hugo Peris: Yeah, absolutely.
We’re continuing to think about

unmet needs in this in this
patient- patient populations.

And, you know, one source of
inspiration, again, this what’s

been happening in the field for
the last few years, we have the

utmost respect for Frequency
Therapeutics, and Otonomy,

Decibel, and the many other
companies that have been trying

to advance treatments for
hearing. We’re also disappointed

by the fact that some of these
companies are no longer focused

on this effort. And, you know,
we still hope that we’ll be able

to overcome those challenges and
be the ones contributing to

advancing this, this therapy. So
beyond the steroid for Meniere’s

that we’re focused on today,
we’re continuing to build a

pipeline, we are very much
committed to the traditional

approaches to drug in the ear.
So gene therapies for now, an

approach that we are not focused
on at Spiral, we think that

small molecules and small
proteins might actually be good

solutions for in a field that,
like Dr. Limb mentioned, there

are no drugs approved yet. So
we’re we’re committed to

advancing those type of
developments. And we’re looking

at a range of neuroprotective
otoprotective assets that could

help us address different types
of hearing loss from

chemotherapy-induced to age
related noise-induced. So we’re

very much excited about all
these other all these

opportunities, recognizing that,
you know, these are very, not

well defined patient
populations, where there’s still

a lot more work to do in terms
of identifying who are the

patients that have are more more
likely most likely to respond to

this type of treatments. And,
you know, we also believe that

the field has made a lot of
progress over the last few years

in identifying those patient
populations establishing what

are the right outcome measures,
and we’re going to try to learn

upon those things and, and
implement them into our studies

so that we can be more precise
in the development of our

treatments.

Brian Taylor: Yeah, that’s
great. We hope to have you back

sometime in the near future. And
you can talk about some of the

other exciting developments that
you have going on.

Charles Limb: Let me just add
one thing to that, you know,

it’s one thing to not have a
medication, but it’s another

thing to have a medication and
not know how to get it to where

it needs to get. And so there’s
a two fold problem, you know,

it’s not likely that a treatment
for the inner ear is going to be

a pill that you just take. And
it’s just, the odds of that

being the solution here are low.
And so it’s very likely that

we’re going to have to deliver
something to a relatively

inaccessible space. The nice
thing about the platform that

we’re building is that it is
somewhat agnostic to the actual

agent, meaning once we have
refined and perfected the

approach, which is very, already
very functional and usable, you

could basically put anything in,
you can deliver almost any agent

physically to where it needs to
get to. And so we’re excited

about not just our own pipeline,
which is great, and they own

storage formulations of SPT
2101. But the concept that any

agent in the future might
benefit from the work with that

we’re doing you know, this is
when you try to change a field

that doesn’t happen with just
one small team. And this is kind

of a field wide effort. And so I
think we all have to kind of

join forces and hope that our
work can supplement and

synergize with each other.

Brian Taylor: Yeah, that’s
really interesting. And maybe

you could talk a little bit
about this the delivery

mechanism, I guess, I’m curious
to know, like, what have you

learned over the last six or so
years that your company has been

existing in existence about how
the delivery system? What’s

important about that, what have
you learned? What do you know

now today about it that you
didn’t know five years ago? Can

you speak a little bit?

Charles Limb: I can let me get
into it. Without getting into

too many specifics. I want to
just say that something that

might not be clear to
audiologists but it’s very clear

to otologists. Right now, in the
way the way we treat things

intratympanically, there’s a big
assumption, a number of

assumptions that are made, that
the medication is going to get

to where it needs to. But if you
actually break down each of

those assumptions, and then look
at the potential obstacles, what

you learn is there are many
obstacles that are preventing

right now standard intratympanic
therapy from getting into the

cochlea. And so what we have
sort of resorted to is, I mean,

if you’re probably very aware of
this today, we just blindly

stick needles into the eardrum
and hope that somehow the what’s

in the syringe lands in the
cochlea, inside the cochlea,

that’s, that’s not a given, you
know, there’s there’s pseudo

membranes, there’s air bubbles,
there’s redirection, there’s

like clearance down the
Eustachian tube, there’s like

the medication can be nowhere
near the round window, by the

time the patient walks out of
the clinic. And so we need some

certainty, some assurances that
the medicine is first being

placed to where you need it at
the round window, which is the

best apparent entry point into
cochlea. But also Furthermore,

that there’s durability, that
over time, you know, the patient

is not going to swallow their
lunch and then find that the

medication is suddenly gone. Now
that there needs to be some

persistence of this medication
where you want it. And so we’re

working on all of the above
minimally invasively, how to

deliver that to the round window
in a durable way.

Brian Taylor: That’s great. And
my last question, and I think I

already kind of, sort of know
the answer based on our

conversation, and that is, if
you have a crystal ball, and

these treatments are proven to
be successful in your clinical

trials, how do you see them
changing the way that otology is

practiced in the clinic?

Charles Limb: I think otology is
desperate for more solutions,

you know, think about the
patient that comes in with some

central hearing loss that we see
all the time, every week, I see

this in my clinic. And what we
have to offer them is just

really not not very reassuring,
it’s a hope. And what I think

will happen is a new generation
of procedural interventions,

where you’re not just getting a
pill, you’re not or you’re not

going to the OR, there’s
something in between, it’s an

office based procedure that
offers a much higher likelihood

of control. And, you know, some
of the benefits that we’re

hoping for are really based on
advances, advances that were

well established in
ophthalmology, which as a field

are, I would say, is quite ahead
of otology. And much of Spiral’s

roots really are in opthamologic
advances because some of our

scientific founders had
ophthalmology backgrounds, and

they were doing things that
otologists really could could

learn from. And so our hope is
that a lot of the procedural

based things in the clinic that
would help somebody with hearing

loss which don’t exist, will
spawn a kind of new generation

of kind of mid level
interventions that I think would

be very helpful.

Brian Taylor: Right. And you go
any final thoughts before we

wrap things up?

Hugo Peris: Just thank you for
the time. Thank you for the

opportunity to talk about spiral
and explain a little bit about

the work we’ve been doing. We’re
very passionate about the field.

We the thing that there are many
unmet needs. Were excited about

this opportunity to advance the
field to introduce innovations.

And we’re just going to continue
to work hard to bring this drugs

closer to patients.

Brian Taylor: That’s great. Hugo
Peris and Dr. Charles them of

Spiral Therapeutics. Thanks for
your time. We really appreciate

you being with us today. At This
Week in Hearing