Key Highlights in interstitial lung disease: Insights from ATS 2026

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OK,
so in the in the interest of everybody's

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time, we only have an hour together.

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So I think we should just go ahead and
get started.

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Hi everybody.

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Thanks for joining tonight's ILD
Masterclass hosted by myself, Leigh Minuk.

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I'm a respirologist at Vancouver General
Hospital and and I also work through

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University of British Columbia.

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Today the presentation title is Key
Highlights in Interstitial Lung Disease

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and we'll be hearing all about that from
Doctor Jolene Fisher.

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And it's,
it's really a pleasure to introduce

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Doctor Fisher.

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She's a long time mentor of mine and
somebody who I've always really looked up

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to.

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She's a respirologist and clinician
investigator at University Health Network.

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She's also the research director of the
Interstitial Lung Disease program and an

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associate professor at the University of
Toronto and an excellent one at that.

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She received her Doctor of Medicine and
Internal Medicine residency training from

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the University of Manitoba and then she
completed her respirology residency,

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interstitial lung disease Fellowship and
Masters of Science in Clinical

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Epidemiology and Healthcare Research at
the University of Toronto,

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where she stayed and now holds her
faculty position.

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Her research interests include
interstitial lung diseases,

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health services research registry and
outcomes research.

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So that's a brief bio on on Doctor Fisher.

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I could of course say more.

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I do want to cover a few housekeeping
items if we can just go to the next slide.

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So thanks for participating everyone in
this program.

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Just make sure that you know if you want
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If you want to turn it on,
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You can utilize the chat box throughout
the presentation,

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so feel free to type any questions in the
chat.

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I'll try to bring some of those questions
up as we get through topics if they're

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written in the chat,
but we ask that you keep your microphone

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muted until the very end when there's an
opportunity to speak out loud.

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Ask questions yourself toward the end of
the program,

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but just for the interest of time,
we ask you to hold some of those

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questions,
the verbal questions until the end.

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And then just a reminder,
it's very helpful to get your evaluations

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of these events.

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So if you can,
please complete the evaluation at the end

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and provide some feedback to help shape
future programs that would be amazing.

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And then next slide,
it's also important to just note here

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that this program has received some
financial support from Boehringer and the

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faculty has received an honorarium for
their participation.

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Next slide, and this is,
these are my disclosures.

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You can go to the next slide.

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And these are Doctor Fisher's disclosures.

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And now it's my pleasure to pass things
over to Doctor Fisher to tell us all

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about what she learned at ATS.

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All right.

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Well, thanks so much, Leigh,
and thank you for the lovely introduction.

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So today's learning objectives are to
understand some of the key highlights and

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latest advancements in ILD that were
presented at ATS.

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This year.

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I'll review and interpret some of the
outcome and key data from some trials

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that were presented.

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And ideally,
we want to assess the clinical relevance

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and potential impact of these findings on
the care of our patients.

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So I identified a few ATS themes that
I'll cover.

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So one was clinical trials.

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I'm going to talk about inhaled
troposinol, LPA1 antagonist,

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nerandomilast and extended release
nalbuphine.

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I'm going to talk about interstitial lung
abnormalities with a focus on screening

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and risk stratification.

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And lastly talk about quantitative CT or
QCT.

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So starting with inhaled treprostinil.

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Inhaled treprostinil has been shown to
have activity across fibrotic,

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vascular and inflammatory pathways and it
activates multiple prostenoid receptors

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and lung fibroblasts,
resulting in attenuation of lung fibrosis.

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Hopefully Martin is on and if you have
any further questions you can direct them

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towards him.

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And a post-hoc analysis of the 16 week
increase study,

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which was in patients with ILD and
pulmonary hypertension showed improved

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FVC in patients with ILD including the
IPF subgroup.

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And the figure I'm showing you right here
is from the IPF subgroup.

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And you can see that the line in blue was
inhaled treprostinil showing an increase

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in FVC compared to the placebo group,
which had a decline in FVC.

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So because of all this,
the TETON program was developed,

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which included TETON-1 and TETON-2,
two phase three randomized trials of

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inhaled treprostinil for IPF.

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TETON-2 recruited more quickly and
finished first and has previously been

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published.

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And then the TETON results were presented
at ATS this year and the results of

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TETON-1 and the combined results were
published concurrently in the New England

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Journal of Medicine.

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So the TETON study design included
patients with IPF who were randomized to

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either inhaled treprostinil or placebo.

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The starting dose was three breaths or 18
micrograms 4 times daily and then

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titrated up as tolerated to a target dose
of 12 breaths or 72 micrograms 4 times

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daily.

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IPF diagnosis was confirmed by central
review and FVC had to be at least 45% and

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background antifibrotic therapy was
allowed.

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The primary endpoint was change in
absolute FVC and milliliters from

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baseline to week 52.

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And there were several secondary
endpoints including time to clinical

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worsening, time to 1st exacerbation,
overall survival, change in the baseline,

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change in the percent predicted FVC
compared to baseline at week 52,

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change in K-BILD and change in DCO.

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And this is just the flow diagram showing
patient recruitment and randomization.

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The highlights are that about 600
patients were randomized 1:1 to inhaled

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treprostinil or placebo.

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The week 52 completion rates were similar
between both groups, so around 73%.

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However,
drug discontinuations were numerically

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higher with inhaled treprostinil,
so about 40% versus 33% and that was

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primarily driven by adverse events and
subject withdrawal.

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Here's some of the baseline
characteristics.

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So they were balanced between treatment
groups and patients were our typical IPF

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trial patients, so a little bit older,
in their 70s and male and a mild to

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moderate physiologic impairment.

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And in terms of background therapy,
so approximately 78% of patients were

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receiving background antifibrotic therapy.

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So most of the patients in the trial and
nintedanib was a bit more common than

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pirfenidone.

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And this figure shows the TETON-1 primary
results.

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So the top line in blue is the inhaled
treprostinil group and then the Gray line

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at the bottom is the placebo group.

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And the treprostinil group had about a 43
milliliter decline over the 52 week

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period

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Compared to the placebo group,
which was almost 200 milliliters.

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So there was a treatment difference of
130 milliliters.

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This was statistically significant
favouring inhaled treprostinil and this

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is showing the data broken down by
background antifibrotic therapy.

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So the first panel is patients not
receiving any antifibrotic therapy and

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the group on the left here is the inhaled
treprostinil versus the grey here is

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placebo.

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So again,
you can see that patients receiving

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treprostinil had less FVC decline
compared to placebo and that was

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replicated in those receiving pirfenidone
as well as those receiving background

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nintedanib therapy.

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The difference between groups and those
receiving no antifibrotic therapy was

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around 100 milliliters of lung function
and it was higher in the groups receiving

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antifibrotic therapy.

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So the pirfenidone group was around 168
milliliters versus the nintedanib group

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was around 123.
in terms of the secondary endpoint.

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So the secondary endpoint of time to
clinical worsening,

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which included any of the clinical
worsening events was better in the

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treprostinil group and that was
statistically significant.

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The other statistically significant
change was percent of FVC predicted and

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that again favored treprostinil.

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The other secondary outcomes trended
towards favoring treprostinil,

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but they weren't statistically
significant.

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So in terms of adverse events,
cough was by far the most common adverse

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event and there was more cough in the
treprostinil group.

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So these patients coughed with
treprostinil,

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it was over 50% and other adverse events
that were more common with treprostinil

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included headache,
throat irritation and oropharyngeal pain.

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In terms of total number of adverse
events

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So this was higher in the inhaled
treprostinil group close to 2000 as

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opposed to close to 1800.

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And the total number of serious adverse
events, however,

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was lower in the inhaled treprostinil
group compared to placebo and adverse

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events leading to death was lower in the
inhaled treprostinil group as compared to

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placebo as well.

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So in summary,
TETON-1 met its primary endpoint and

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inhaled treprostinil demonstrated a
statistically significant benefit of 130

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milliliters compared to placebo and FVC
at 52 weeks.

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In terms of the secondary endpoints,
there was a statistically significant

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reduction in risk of clinical worsening
and change in the predicted FVC and then

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just numerical improvement in regards to
acute exacerbation, survival,

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K-BILD and diffusing capacity.

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And in terms of safety and tolerability,
it was generally well tolerated.

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However,
cough was definitely the most common

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adverse event and this did lead to drug
discontinuation.

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And as I had mentioned,
the New England Journal of Medicine

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article did pool TETON-1 and TETON-2 and
this was a prespecified analysis and

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essentially the results from TETON-1 one
and TETON-2 were very similar.

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And so the pooled results did show a
statistically significant benefit in FVC

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decline for inhaled treprostinil with a
delta of around 110 milliliters of lung

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function again.
The secondary endpoint of clinical

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worsening was met.

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And then in the pooled analysis,
there were less acute exacerbations in

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the inhaled treprostinil groups as
compared to placebo.

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Any of you involved in TETON know that
the device,

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which I'm showing a photo of on the right,
the nebulizer was quite large and

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cumbersome and not the kind of thing that
somebody could just throw in their purse

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to take around or throw in a backpack to
take around.

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So I think that was also considered one
of the barriers in the medication.

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However, good news,
there is a DPI formulation available.

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I have a picture of it there on the left.

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It's quite small,
definitely could tuck into a bag pretty

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easily.

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And an equivalency study has already been
done.

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I believe it's called the BREEZE trial,
which did show bioequivalence.

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So hopefully,
if this drug becomes available for our

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patients, we have access to the DPI,
which I think would be a lot more

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feasible for them to use.

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All right, Leigh,
maybe any burning question -- LPA1

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No burning questions in the chat just yet,
So go for it.

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All right, sounds good.

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So next I'm going to talk about LPA1
receptor antagonist.

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So there were two posters presented.

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I've just shown the titles of them here
at ATS that I saw that I'm going to talk

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about.

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Just to give a bit of background.

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So after lung injury you have an increase
in autotaxin and this increases LPA

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signaling and LPA then activates other
receptors that lead to downstream

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signaling resulting in cellular processes
that are involved in driving fibrosis.

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So it's a natural potential target for
anti-fibrotic agents.

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And the first drug I'm going to talk to
you about is Admilparant.

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I never know if I'm saying these
correctly.

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So if anybody knows,
please don't hesitate to to let me know

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if I'm incorrect.

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But Admilparant is a second generation
LPA1 antagonist.

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So it blocks LPA-mediated fibroblast
recruitment.

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And I say second generation.

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So this was developed after there was a
first generation LPA antagonist that was

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basically associated with significant
hepatobiliary toxicity that the resulted

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in discontinuation of that drug
development.

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And so this drug was developed.

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So it doesn't have the same hepatobiliary
toxicity.

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And there was a phase two study that was
already published that was a parallel

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study of IPF and PPF cohorts that was
randomized 1:1:1,

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either 30 milligrams twice daily,
of admilparant,

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60 milligrams twice daily or placebo.

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And the 60 milligram twice daily dose was
shown to reduce FVC decline in patients

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with PPF and IPF.

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And so that led to development of a phase
three program called the ALOFT program

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which is currently underway.

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And so that was some of the initial ALOFT
program was presented at ATS.

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That's what I'm going to talk to you
about now.

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So this was a trial that was 1:1:1
randomization of either Admilparant 60

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milligrams twice daily,
Admilparant 120 milligrams twice daily or

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placebo.

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And the study is a 2 cohort design.

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And so cohort 1 is small and was designed
as a single blind study to evaluate

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safety and tolerability of the 120
milligram dose at 4 weeks since it wasn't

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studied in the phase two.

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And then cohort 2 is your typical
double-blind placebo-controlled

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randomized trial with a much larger
cohort.

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And the primary endpoint was FVC change
at week 52.

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And so this is just some data showing the
inclusion criteria and the randomization.

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So the key inclusion criteria are similar
to a lot of our IPF trials and PPF, sorry,

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IPF trials.

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And so 40 years or older,
IPF had to be verified at screening.

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This one had FVC of 40% or higher and
diffusing capacity of 25% or higher and

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background antifibrotic therapy was
allowed.

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And this is baseline demographic
characteristics of the two cohorts.

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So again remember cohort 1 is small more
of testing safety and then cohort 2 is

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larger, almost 1200 patients.

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And again this is very similar to a lot
of our IPF trials.

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So age around 70, you know,
male predominant,

00:16:46.804 --> 00:16:52.147
and time to diagnosis in years is maybe a
little bit shorter,

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so around 2 years compared to some of our
other IPF trials and maybe a little bit

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less patients on background antifibrotic
therapy,

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but still majority of patients on
background antifibrotic therapy compared

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to those who are on nothing.

00:17:13.520 --> 00:17:16.320
So stay tuned for results of that.

00:17:16.320 --> 00:17:20.412
That's all that was presented at ATS,
just some baseline stuff just to try to

00:17:20.412 --> 00:17:21.200
get us excited.

00:17:21.200 --> 00:17:26.496
But you know we look forward to seeing
the results of that phase three study and

00:17:26.496 --> 00:17:28.720
the Phase 2 results from this one.

00:17:28.720 --> 00:17:33.520
I always have a hard time saying for
Fipaxalparant was presented at ATS.

00:17:34.480 --> 00:17:38.894
I won't belabor this,
but this is a figure showing the primary

00:17:38.894 --> 00:17:44.080
endpoint which was FVC percent predicted
change from baseline to week 52.

00:17:44.080 --> 00:17:49.600
And I'm sure you can see on the graph
already that it was not significant.

00:17:49.600 --> 00:17:56.845
There was no no benefit in the treatment
compared to placebo and the key secondary

00:17:56.845 --> 00:18:02.520
endpoint which was FVC percent predicted
decline of 10% or more.

00:18:02.960 --> 00:18:07.760
And if anything the placebo group seem to
have less FVC decline compared to the

00:18:07.760 --> 00:18:08.720
treatment group.

00:18:08.720 --> 00:18:14.322
So this program has now been just that
has now been terminated because of the

00:18:14.322 --> 00:18:15.400
negative study.

00:18:20.320 --> 00:18:23.240
And I just wanted to put this up here.

00:18:23.240 --> 00:18:27.022
It's, I know,
I don't want you to consider it an

00:18:27.022 --> 00:18:31.113
inclusive list,
but just to show that there are many

00:18:31.113 --> 00:18:36.980
drugs that are either in preclinical
phase or undergoing study or have been

00:18:36.980 --> 00:18:40.840
studied and terminated - that target LPA
pathway.

00:18:40.840 --> 00:18:43.971
So you know,
stays tuned and certainly this is a

00:18:43.971 --> 00:18:46.080
pathway of interest in the field.

00:18:46.080 --> 00:18:53.720
Just pause there for a sec,
take a sip of water.

00:18:53.880 --> 00:18:56.160
Anything Leigh?

00:18:57.200 --> 00:18:59.088
Yeah,
I think people are saving their questions

00:18:59.088 --> 00:18:59.600
till the end.

00:18:59.600 --> 00:19:03.642
So you're going to get inundated with a
lot of a lot of questions, you know,

00:19:03.642 --> 00:19:04.640
cameras on unmuted.

00:19:04.640 --> 00:19:06.200
So it's perfect, perfect.

00:19:06.200 --> 00:19:06.640
I can't wait.

00:19:06.640 --> 00:19:09.000
I'm saving time for questions,
so store them up.

00:19:10.320 --> 00:19:10.600
OK.

00:19:11.520 --> 00:19:14.224
All right,
so let's talk about Nerandomilast and the

00:19:14.224 --> 00:19:14.480
last.

00:19:17.320 --> 00:19:21.440
So this is the FIBRONEER-IPF study.

00:19:22.000 --> 00:19:25.049
I think many people on this call are
already aware of this data,

00:19:25.049 --> 00:19:28.240
which was published in the New England
Journal of Medicine in 2025.

00:19:28.680 --> 00:19:33.746
You may ask why am I talking about it,
but it was talked about ATS 2026 and

00:19:33.746 --> 00:19:37.080
there were also some post-hoc analyses
presented.

00:19:37.080 --> 00:19:41.800
So I am going to spend a little bit of
time just refreshing our memory.

00:19:41.800 --> 00:19:46.743
So starting with FIBRONEER-IPF,
this was a phase three study of almost

00:19:46.743 --> 00:19:51.826
1200 patients with IPF who were
randomized to nerandomilast 9 milligrams

00:19:51.826 --> 00:19:55.586
twice daily,
18 milligrams twice daily or placebo for

00:19:55.586 --> 00:19:56.840
at least 52 weeks.

00:19:57.840 --> 00:20:02.240
The patient population was IPF by ATS
criteria.

00:20:02.720 --> 00:20:07.480
FVC of at least 45% and a DCO of 25%
predicted.

00:20:07.760 --> 00:20:10.560
And patients were stratified by
background therapy.

00:20:10.560 --> 00:20:15.960
So they were stratified to no background
therapy, pirfenidone or nintedanib.

00:20:16.000 --> 00:20:20.960
And the primary endpoint was change in
FVC in milliliters at 52 weeks.

00:20:20.960 --> 00:20:25.263
And then the key secondary endpoint was a
composite of time to 1st exacerbation,

00:20:25.263 --> 00:20:27.920
hospitalization for a respiratory cause
or death.

00:20:31.280 --> 00:20:37.120
And so this is the primary endpoint
result in the overall population.

00:20:37.120 --> 00:20:42.720
So the line in green is the 18 milligram
twice daily nerandomilast dose.

00:20:43.800 --> 00:20:47.975
The bluey purpley gray line is the
nerandomilast 9 milligrams twice daily

00:20:47.975 --> 00:20:50.120
and then the gray line is the placebo.

00:20:50.120 --> 00:20:53.329
So as you can see,
patients who were receiving either dose

00:20:53.329 --> 00:20:57.190
of nerandomilast had less FVC decline
compared to placebo and this was

00:20:57.190 --> 00:21:00.399
statistically significant and it met its
primary endpoint.

00:21:01.000 --> 00:21:04.692
When we look at this data based on
background therapy,

00:21:04.692 --> 00:21:10.331
patients who are on no background therapy
had a benefit on nerandomilast both the 9

00:21:10.331 --> 00:21:12.480
milligram and 18 milligram dose.

00:21:13.320 --> 00:21:18.317
Patients who are on background nintedanib
therapy again also had a benefit in

00:21:18.317 --> 00:21:21.200
either the 9 milligram or 18 milligram
dose.

00:21:21.200 --> 00:21:25.602
And then what I just want to highlight
for you is those patients who were on

00:21:25.602 --> 00:21:30.234
background pirfenidone who did not have a
benefit with a 9 milligram twice daily

00:21:30.234 --> 00:21:30.520
dose.

00:21:30.520 --> 00:21:35.791
And it was subsequently found that
pirfenidone essentially decreases the

00:21:35.791 --> 00:21:39.185
levels,
the serum levels of nerandomilast such

00:21:39.185 --> 00:21:44.239
that the 9 milligram dose was like
patients weren't getting anything.

00:21:44.240 --> 00:21:46.120
It was as though they were getting
placebo.

00:21:47.040 --> 00:21:50.240
So 9 milligram dose does not work if
you're on pirfenidone.

00:21:54.680 --> 00:21:59.224
In terms of adverse events,
I'm just showing both the FIBRONEER-IPF

00:21:59.224 --> 00:22:04.304
and FIBRONEER-ILD together to highlight
that diarrhea was the most frequent

00:22:04.304 --> 00:22:05.240
adverse event.

00:22:05.720 --> 00:22:12.272
I will say that it was much more common
in patients who were getting both

00:22:12.272 --> 00:22:14.840
nintedanib and nerandomilast.

00:22:15.720 --> 00:22:21.791
nerandomilast alone without antifibrotic,
other antifibrotic therapy did have a

00:22:21.791 --> 00:22:25.661
small an increase in diarrhea compared to
placebo,

00:22:25.661 --> 00:22:29.760
but much less than that which we see with
nintedanib.

00:22:29.760 --> 00:22:32.520
So our hope is,
and certainly in talking to our

00:22:32.520 --> 00:22:35.914
colleagues that are already using
nerandomilast in the US,

00:22:35.914 --> 00:22:39.480
it does seem like it's much better
tolerated than nintedanib.

00:22:39.480 --> 00:22:41.840
So I think we're all pretty excited about
that.

00:22:46.040 --> 00:22:52.000
This is some post-hoc subgroup analysis
data that was presented at ATS this year.

00:22:52.520 --> 00:23:00.949
And this is the 18 milligram daily dose
and assessing the effect on change in FVC

00:23:00.949 --> 00:23:02.080
at week 52.

00:23:02.400 --> 00:23:05.327
And you can see there's all these
different groups,

00:23:05.327 --> 00:23:08.480
so stratified based on lung function
percent predicted,

00:23:08.480 --> 00:23:12.760
so greater than 90 all the way down to
less than 50, GAP stage at baseline.

00:23:12.760 --> 00:23:14.000
So how severe are they?

00:23:14.000 --> 00:23:15.840
And then time to diagnosis.

00:23:15.840 --> 00:23:19.920
And really the take home here is that
everything is landing on the side

00:23:19.920 --> 00:23:21.280
favouring nerandomilast.

00:23:21.280 --> 00:23:23.160
So obviously this is post-hoc data.

00:23:23.160 --> 00:23:26.346
We have to, you know,
understand that it's hypothesis

00:23:26.346 --> 00:23:29.355
generating,
but it's all supportive of the primary

00:23:29.355 --> 00:23:32.128
outcome,
which is that nerandomilast slows FVC

00:23:32.128 --> 00:23:32.600
decline.

00:23:38.320 --> 00:23:41.476
All right,
So I'm just gonna very quickly show you

00:23:41.476 --> 00:23:44.200
the data in progressive pulmonary
fibrosis.

00:23:44.200 --> 00:23:45.520
So FIBRONEER-ILD

00:23:46.320 --> 00:23:50.355
So again this was also a phase three
study of almost 1200 patients and

00:23:50.355 --> 00:23:54.617
patients who had non-IPF progressive
fibrotic ILD and they used these same

00:23:54.617 --> 00:23:57.800
criteria as INBUILD to define progressive
fibrotic ILD.

00:23:57.880 --> 00:24:01.432
And again,
patients who had the same randomization

00:24:01.432 --> 00:24:06.308
to either the 9 milligram,
18 milligram dose or placebo for 52 weeks,

00:24:06.308 --> 00:24:08.120
same FVC and DCO cut offs.

00:24:08.280 --> 00:24:10.520
Again background nintedanib was allowed.

00:24:11.520 --> 00:24:16.333
And patients who were on prednisone more
than 15 milligrams, mycophenolate,

00:24:16.333 --> 00:24:19.880
tocilizumab, rituximab,
cyclophosphamide were excluded.

00:24:19.880 --> 00:24:22.920
This was same as as the INBUILD study.

00:24:23.960 --> 00:24:27.019
And again,
the primary endpoint was change in FVC at

00:24:27.019 --> 00:24:31.118
week 52 and then it had the same key
secondary endpoint of time to 1st

00:24:31.118 --> 00:24:34.293
exacerbation,
hospitalization for respiratory cause or

00:24:34.293 --> 00:24:34.640
death.

00:24:36.080 --> 00:24:42.600
And the primary endpoint was also met in
terms of change in FVC at 52 weeks.

00:24:42.600 --> 00:24:47.407
And you can see the top 2 lines are the 9
milligram and 18 milligram dose of

00:24:47.407 --> 00:24:50.280
nerandomilast and the bottom line is
placebo.

00:24:50.280 --> 00:24:55.765
So nerandomilast also slowed FVC decline
in patients with non IPF progressive

00:24:55.765 --> 00:24:56.680
fibrotic ILD.

00:25:00.440 --> 00:25:04.851
And again this is just the data showing
no background nintedanib versus

00:25:04.851 --> 00:25:06.200
background nintedanib.

00:25:06.200 --> 00:25:10.212
And the take home message here is that
again,

00:25:10.212 --> 00:25:15.360
it works as upfront monotherapy or as
combination therapy.

00:25:21.720 --> 00:25:25.870
And this is another post-hoc subgroup
analysis of the effect of the 18

00:25:25.870 --> 00:25:29.320
milligram dose of nerandomilast on FVC
change at 52 weeks.

00:25:29.320 --> 00:25:32.100
And again,
it's all the same subgroups in terms of

00:25:32.100 --> 00:25:34.880
lung function,
GAP stage and time since diagnosis.

00:25:34.880 --> 00:25:38.240
And you can see everything is landing on
the side favoring nerandomilast.

00:25:38.240 --> 00:25:42.861
So again, I take this as,
you know supportive of the primary

00:25:42.861 --> 00:25:48.316
outcome and no reason to not use it in
patients who have not, you know,

00:25:48.316 --> 00:25:53.922
better lung function compared to worse
lung function earlier versus later

00:25:53.922 --> 00:25:54.680
diagnosis.

00:26:00.280 --> 00:26:04.418
All right,
So maybe I'll just pivot now to

00:26:04.418 --> 00:26:06.440
nalbuphine for cough.

00:26:09.000 --> 00:26:13.099
So I think we all,
acknowledge there's a real unmet need for

00:26:13.099 --> 00:26:18.409
cough treatment in our patients and we
know chronic cough affects up to 80% of

00:26:18.409 --> 00:26:23.786
our patients with IPF and it's really
associated with impaired quality of life,

00:26:23.786 --> 00:26:27.751
disease progression,
poor outcomes and there's no approved

00:26:27.751 --> 00:26:32.120
therapy specifically indicated for IPF
associated chronic cough.

00:26:33.440 --> 00:26:37.753
And in 2023,
the CANAL study was published,

00:26:37.753 --> 00:26:44.713
which was a phase two randomized
placebo-controlled crossover study of

00:26:44.713 --> 00:26:50.400
around 40 patients looking at extended
release nalbuphine

00:26:50.400 --> 00:26:56.453
And they found in this study that it
significantly decreased objective cough

00:26:56.453 --> 00:26:57.240
frequency.

00:26:57.880 --> 00:27:02.446
And because of this the - it led to
design of a larger study which I'm going

00:27:02.446 --> 00:27:07.191
to talk to you about now that some of the
data is previously published and then

00:27:07.191 --> 00:27:08.200
presented at ATS.

00:27:08.600 --> 00:27:13.867
And in terms of a mechanistic rationale,
so nalbuphine extended release is a Kappa

00:27:13.867 --> 00:27:18.628
opioid receptor agonist and a mu opioid
receptor antagonist that modulates

00:27:18.628 --> 00:27:21.040
central and peripheral cough pathways.

00:27:21.560 --> 00:27:28.464
And because it's a mu opioid antagonist,
it potentially avoids some of the

00:27:28.464 --> 00:27:34.080
traditional limitations of mu opioid
agonists like morphine.

00:27:34.080 --> 00:27:38.200
So that includes the respiratory
depression or the euphoria or addiction.

00:27:40.000 --> 00:27:41.200
So that's the rationale.

00:27:41.360 --> 00:27:46.600
And so this was the CORAL study which was
published earlier in 2026 in JAMA.

00:27:47.240 --> 00:27:55.229
And this was a randomized control trial
of 165 patients with IPF and they were

00:27:55.229 --> 00:28:01.600
randomized to three different doses of
nalbuphine and placebo.

00:28:02.080 --> 00:28:09.120
And the doses were 27 milligrams twice
daily, 54 twice daily or 108 twice daily.

00:28:09.560 --> 00:28:14.528
And the primary outcome was relative
change from baseline and 24 hour cough

00:28:14.528 --> 00:28:19.040
frequency that was measured by a digital
cough monitor at six weeks.

00:28:19.040 --> 00:28:22.040
And the results you can see on the right
of this slide.

00:28:22.040 --> 00:28:28.384
So all three doses of the nalbuphine
decreased cough frequency and they were

00:28:28.384 --> 00:28:34.400
statistically significant in terms of
their benefit compared to placebo.

00:28:34.640 --> 00:28:40.363
And there did seem to be some dose
response with the lowest effect seen in

00:28:40.363 --> 00:28:46.240
the 27 milligram dose and the highest
effect seen in the 108 milligram dose.

00:28:46.240 --> 00:28:49.120
So I think this is really great.

00:28:49.200 --> 00:28:52.551
We have,
obviously medications that slow lung

00:28:52.551 --> 00:28:56.559
function decline,
but that's not what our patients are

00:28:56.559 --> 00:28:58.600
complaining about in clinic.

00:28:59.440 --> 00:29:03.870
And so it's great to have treatment that
can, you know,

00:29:03.870 --> 00:29:06.560
potentially target their symptoms.

00:29:10.920 --> 00:29:15.080
All right,
so that's all I'm going to talk about in

00:29:15.080 --> 00:29:17.080
terms of clinical trials.

00:29:17.080 --> 00:29:19.496
So, Leigh,
I don't know if there's any questions

00:29:19.496 --> 00:29:23.342
that have come up that you want me to
address or I can just change courses to

00:29:23.342 --> 00:29:24.919
interstitial lung abnormalities.

00:29:25.360 --> 00:29:27.632
No,
there are there are a couple questions

00:29:27.632 --> 00:29:28.320
that came in.

00:29:28.320 --> 00:29:32.099
So the first one is from Daniel Marinescu
about TETON,

00:29:32.099 --> 00:29:36.360
and he noted these trials excluded
patients with obstruction,

00:29:36.360 --> 00:29:41.790
but there's concurrent data out there for
inhaled treprostinil in COPD with PH

00:29:41.790 --> 00:29:46.120
where the trial was discontinued early
due to signal for harm.

00:29:46.120 --> 00:29:49.360
So the perfect trial in ERJ,
so we have mixed signal.

00:29:49.360 --> 00:29:55.776
So it's helpful if you have pure ILD,
but in COPD with PH it seems to be

00:29:55.776 --> 00:29:56.480
harmful.

00:29:56.480 --> 00:30:01.479
So his question is your thoughts on how
we should think about emphysema and ILD,

00:30:01.479 --> 00:30:06.169
CPFE patients and whether or not we
should use treprostinil in them and and

00:30:06.169 --> 00:30:09.502
should we err on the side of caution or
are we being,

00:30:09.502 --> 00:30:14.440
would we be being overly cautious and
whether or not that was discussed at ATS?

00:30:15.160 --> 00:30:16.320
Yeah, that's a great question.

00:30:16.320 --> 00:30:20.080
Actually I don't,
I'm not sure if Shane is on the call.

00:30:20.080 --> 00:30:23.720
He was at ATS as well if he was at any
sessions where that came up,

00:30:23.720 --> 00:30:26.880
but I don't recall being at any sessions
where it came up.

00:30:26.880 --> 00:30:32.782
But it's a great question, you know,
and I always wonder sometime with these

00:30:32.782 --> 00:30:37.458
inhaled therapies too,
depending on the solutions, you know,

00:30:37.458 --> 00:30:42.133
with our COPD patients,
especially ones that have, you know,

00:30:42.133 --> 00:30:45.200
very severe obstruction or bronchospasm.

00:30:45.400 --> 00:30:48.025
You know,
I always worry about some of these

00:30:48.025 --> 00:30:51.000
inhaled drugs potentially increasing
bronchospasm.

00:30:51.000 --> 00:30:53.680
So it's something that, you know,
would maybe be in the back of my head.

00:30:53.680 --> 00:30:58.003
But, you know,
I think that if somebody was very

00:30:58.003 --> 00:31:04.269
emphysema predominant, you know,
probably I wouldn't be jumping to put

00:31:04.269 --> 00:31:08.240
them on this therapy if I have access to
it.

00:31:09.320 --> 00:31:11.967
But I think, you know,
in my patient who was very fibrotic

00:31:11.967 --> 00:31:14.391
predominant with a little bit of
emphysema, you know,

00:31:14.391 --> 00:31:17.801
maybe I would be paying a little bit
closer attention or I'd have it in the

00:31:17.801 --> 00:31:18.520
back of my mind.

00:31:18.520 --> 00:31:23.779
But I, I, I don't think I would, you know,
just 'cause they have a bit of emphysema,

00:31:23.779 --> 00:31:25.760
say no, definitely not using it.

00:31:26.040 --> 00:31:31.659
But if their primary physiology was
obstructive and I felt they were more

00:31:31.659 --> 00:31:35.760
emphysema,
maybe I would be be less likely to use it.

00:31:35.760 --> 00:31:38.880
But I'd be interested what others thought.

00:31:38.880 --> 00:31:42.977
Maybe they could text that in the chat
for now and you can let us know after

00:31:42.977 --> 00:31:44.840
what what people what people think.

00:31:45.960 --> 00:31:47.480
Yeah, I think I agree with that too.

00:31:47.480 --> 00:31:50.639
You know, the more that I reflect on it,
if they're, you know,

00:31:50.639 --> 00:31:54.000
overtly obstructive or severely
emphysematous, I'd probably avoid.

00:31:54.000 --> 00:31:57.818
It's going to be those people I think
that are in the sort of in between that

00:31:57.818 --> 00:32:01.685
you kind of debate a little bit more and
and certainly if they're exacerbating

00:32:01.685 --> 00:32:04.280
quite often that that'd be something to
worry about.

00:32:06.520 --> 00:32:07.400
Gokul asked.

00:32:08.040 --> 00:32:10.286
Jolene,
can you remind me if there's an extension

00:32:10.286 --> 00:32:10.960
phase to Teton?

00:32:10.960 --> 00:32:14.503
And if so,
was were there any data presented on FVC

00:32:14.503 --> 00:32:16.480
trends over that longer term?

00:32:17.800 --> 00:32:21.682
I didn't see any of the longer term data
presented,

00:32:21.682 --> 00:32:27.432
but I suspect that that's going to be
coming like that'll probably be coming

00:32:27.432 --> 00:32:29.000
out in the next year.

00:32:29.000 --> 00:32:33.788
And then presented at, you know,
ATS 2027 kind of how we saw saw with

00:32:33.788 --> 00:32:38.235
FIBRONEER, but but yeah,
I didn't I didn't see any else any else

00:32:38.235 --> 00:32:38.920
presented.

00:32:40.280 --> 00:32:43.240
And then last on the topic of of TETON.

00:32:43.600 --> 00:32:45.720
And then there was one question about
nalbuphine.

00:32:46.360 --> 00:32:50.920
Shane said lots of discussion about TETON,
but the PERFECT trial wasn't discussed.

00:32:51.320 --> 00:32:54.200
But it'll be interesting to see what will
be on the product monograph.

00:32:54.200 --> 00:32:54.840
And that's true.

00:32:54.840 --> 00:32:59.624
I mean some of that will be informed by
by what the drug companies warn us not to

00:32:59.624 --> 00:32:59.800
do.

00:33:03.280 --> 00:33:08.840
And then just over to [Gillian Goobie]
asked if there's any access to nalbuphine

00:33:08.840 --> 00:33:14.400
extended release in Canada and a couple
of comments that no, not, not quite yet.

00:33:14.400 --> 00:33:16.880
My understanding is that that it's not
available.

00:33:17.440 --> 00:33:19.120
Yeah, that's my understanding as well.

00:33:19.120 --> 00:33:22.960
Certainly like not in an outpatient kind
of setting anyway.

00:33:25.520 --> 00:33:25.640
OK.

00:33:25.680 --> 00:33:29.807
Oh, and then Daniel had another question,
just a a logistics question around

00:33:29.807 --> 00:33:31.040
treprostinil and TETON.

00:33:31.320 --> 00:33:33.960
He mentioned he wasn't aware there was a
DPI version.

00:33:35.280 --> 00:33:39.200
Is this now able to go through for
approval by the FDA or the CDA?

00:33:39.200 --> 00:33:43.486
Because there's a phase three trial out
there by Insmed looking at treprostinil

00:33:43.486 --> 00:33:45.040
and ILD with a DPI formation.

00:33:45.840 --> 00:33:49.810
Wouldn't it be strange if United can come
to market with a DPI while others have to

00:33:49.810 --> 00:33:51.560
run or continue separate phase three?

00:33:53.120 --> 00:33:55.956
Yeah,
so we did talk about this with some of

00:33:55.956 --> 00:34:00.872
the companies at ATS and it sounds so
they did do bio equivalent studies with

00:34:00.872 --> 00:34:01.439
the DPIs.

00:34:01.440 --> 00:34:06.894
And so that is sufficient apparently for
the FDA and I assume hopefully for Health

00:34:06.894 --> 00:34:07.880
Canada as well.

00:34:07.880 --> 00:34:13.213
So the initial thinking right now is that
they're not going to have to do,

00:34:13.213 --> 00:34:17.480
you don't have to do another phase three
study for the DPI.

00:34:18.960 --> 00:34:20.520
OK, that's, that's really good to know.

00:34:22.000 --> 00:34:26.589
And then Shane just made one last comment
that at least nalbuphine subcutaneous is

00:34:26.589 --> 00:34:30.958
available in a hospital setting and it
was tried once but didn't work and hard

00:34:30.958 --> 00:34:33.999
to interpret with a different
pharmacokinetic profile,

00:34:33.999 --> 00:34:35.880
which is an interesting side note.

00:34:36.840 --> 00:34:38.000
Yeah, fair enough.

00:34:38.680 --> 00:34:39.400
OK, great.

00:34:39.400 --> 00:34:41.720
So I'll let you I'll let you keep going.

00:34:41.720 --> 00:34:43.760
But that's that's it for the questions
for now.

00:34:44.320 --> 00:34:45.320
OK, great.

00:34:45.360 --> 00:34:50.030
So I'll change courses now to talk about
interstitial lung abnormalities,

00:34:50.030 --> 00:34:53.501
which was, I don't know if,
I don't know if, you know,

00:34:53.501 --> 00:34:57.920
calling it a hot topic is fair,
but it was talked a lot about at ATS.

00:34:57.920 --> 00:35:03.381
And so I think a lot of the discussion
obviously stems from the fact that this

00:35:03.381 --> 00:35:08.360
document was recently published,
which was a clinical statement by ATS.

00:35:08.760 --> 00:35:14.479
Some of the authors are probably on this
call so they can chime in at any time,

00:35:14.479 --> 00:35:19.483
but and which was basically providing
guidance on the approach to the

00:35:19.483 --> 00:35:25.202
evaluation and management of interstitial
lung abnormalities and just to remind

00:35:25.202 --> 00:35:28.919
ourselves what interstitial lung
abnormalities are.

00:35:28.920 --> 00:35:32.149
So according to the ATS,
they're non dependent bilateral

00:35:32.149 --> 00:35:36.398
parenchymal abnormalities on a CT
involving at least 5% of a lung zone and

00:35:36.398 --> 00:35:40.477
they can include ground glass opacities,
reticulation, lung distortion,

00:35:40.477 --> 00:35:42.800
traction bronchiectasis and honeycombing.

00:35:43.160 --> 00:35:46.253
But they don't,
patients don't yet meet the criteria area

00:35:46.253 --> 00:35:46.680
for ILD.

00:35:48.120 --> 00:35:52.925
And so and you know,
before Shane plugs in his question about

00:35:52.925 --> 00:35:58.427
the footnote in the table here,
which says if they have a probable UIP

00:35:58.427 --> 00:36:03.000
pattern or a UIP pattern,
then it's ILD as opposed to ILA.

00:36:03.120 --> 00:36:07.448
And so he, he, I think like many of us,
found that to be a little bit

00:36:07.448 --> 00:36:12.148
contradictory because if you have
traction bronchiectasis and honeycombing,

00:36:12.148 --> 00:36:14.560
then that is a probable or UIP pattern.

00:36:14.560 --> 00:36:20.096
But I think the spirit of the message and
talking to some of the authors is that,

00:36:20.096 --> 00:36:23.473
you know,
basically a probable UIP pattern should

00:36:23.473 --> 00:36:28.334
have enough of these traction
bronchiectasis changes to feel like it is

00:36:28.334 --> 00:36:29.280
an actual ILD.

00:36:29.360 --> 00:36:31.200
So I know a little bit nebulous.

00:36:31.200 --> 00:36:36.120
I'm sure this will be revised in multiple
guideline revisions to come.

00:36:36.120 --> 00:36:39.200
But right now this is our definition of
ILA.

00:36:40.040 --> 00:36:41.880
And so why do we care about ILAs?

00:36:41.880 --> 00:36:43.920
Well, we know that a lot of them progress.

00:36:43.920 --> 00:36:49.240
So over 50% demonstrate radiographic
progression over five years.

00:36:49.240 --> 00:36:52.600
So typically about 10 progress annually.

00:36:53.240 --> 00:36:58.509
And when you look at all the data and it
is associated with accelerated lung

00:36:58.509 --> 00:37:02.000
function decline as well as higher
mortality risk.

00:37:02.000 --> 00:37:08.387
So really the key message is that ILA may
represent an early asymptomatic stage of

00:37:08.387 --> 00:37:10.080
fibrotic lung disease.

00:37:10.080 --> 00:37:14.751
And if we can identify those individuals
at high risk for progression,

00:37:14.751 --> 00:37:19.817
then maybe it creates this opportunity
where we can intercept in the disease

00:37:19.817 --> 00:37:24.160
course before they go on to develop a
clinically significant ILD.

00:37:27.240 --> 00:37:30.800
There were several ILA related themes at
ATS.

00:37:30.800 --> 00:37:35.920
So a big one was really this earlier
identification of fibrotic lung disease.

00:37:35.920 --> 00:37:38.040
So is it a potential intervention window?

00:37:38.800 --> 00:37:42.000
Is there a role for current antifibrotic
therapies in ILA?

00:37:42.000 --> 00:37:46.080
Should we be starting our antifibrotic
therapies as soon as someone has ILA?

00:37:47.320 --> 00:37:50.640
Can we use biomarkers to drive risk
stratification?

00:37:50.640 --> 00:37:54.864
So can we use genetic markers?
Can we use circulating biomarkers to try

00:37:54.864 --> 00:37:59.500
to identify those patients who are at
higher risk for progression and pay more

00:37:59.500 --> 00:38:02.199
attention to them or intervene early on
them?

00:38:02.640 --> 00:38:08.321
And there was a lot of interest in
imaging and AI based risk stratification

00:38:08.321 --> 00:38:08.920
as well.

00:38:10.360 --> 00:38:17.040
So I wanted to - I just picked a couple
abstracts to highlight.

00:38:17.400 --> 00:38:21.000
There were several that had similar
themes.

00:38:21.680 --> 00:38:25.160
I thought that this one was a neat study.

00:38:25.160 --> 00:38:31.031
And so this was a study looking at
proteins that were associated with

00:38:31.031 --> 00:38:37.574
interstitial lung abnormalities and
interstitial lung abnormalities that were

00:38:37.574 --> 00:38:42.440
fibrotic as opposed to non fibrotic as
well as mortality.

00:38:42.440 --> 00:38:46.480
And so this study used for cohorts.

00:38:46.480 --> 00:38:52.968
So the main cohort was the COPD gene
cohort and they used that cohort to

00:38:52.968 --> 00:39:00.080
identify proteins that were associated
with ILA and fibrotic ILA and mortality.

00:39:00.520 --> 00:39:05.025
And then they,
they basically used the other cohorts to

00:39:05.025 --> 00:39:07.680
try and replicate their findings.

00:39:07.680 --> 00:39:13.040
So they used the AGES-REYKJAVIK cohort,
the SPIROMICS and the Framingham cohort.

00:39:13.040 --> 00:39:18.448
And essentially the key findings were
they identified 230 proteins that were

00:39:18.448 --> 00:39:21.680
associated with ILA and the COPD gene
cohort.

00:39:22.000 --> 00:39:26.695
And when they went on to do the meta
analysis and the replication cohort,

00:39:26.695 --> 00:39:31.707
they were able to replicate 159 of those
proteins and they found nine specific

00:39:31.707 --> 00:39:36.720
proteins in these cohorts that were
associated specifically with fibrotic ILA.

00:39:37.120 --> 00:39:41.390
And then of these nine,
they found five that were associated with

00:39:41.390 --> 00:39:43.720
mortality across all of the cohorts.

00:39:44.600 --> 00:39:46.200
And so I thought that that was kind of
interesting.

00:39:46.200 --> 00:39:50.644
So essentially,
they identified 5 proteins associated

00:39:50.644 --> 00:39:53.360
with ILA, fibrosis and mortality.

00:39:53.640 --> 00:39:58.414
And the thought was that maybe you can
develop a protein signature or these

00:39:58.414 --> 00:40:02.811
biomarkers that identify patients at
highest risk for progression and

00:40:02.811 --> 00:40:03.440
mortality.

00:40:03.720 --> 00:40:06.847
And you know,
I think this is a big problem for us

00:40:06.847 --> 00:40:10.955
where there's a lot of ILA,
some of it is going to not do anything

00:40:10.955 --> 00:40:13.960
for many years,
some of it is going to progress.

00:40:13.960 --> 00:40:14.440
And so.

00:40:14.600 --> 00:40:16.764
Obviously,
it would be nice if we had ways to

00:40:16.764 --> 00:40:20.339
restratify these patients and know who
should we be following more closely,

00:40:20.339 --> 00:40:22.879
who should we have a lower threshold to
intervene on.

00:40:28.380 --> 00:40:34.940
So this was another study in ILA looking
at quantitative CT parameters to predict

00:40:34.940 --> 00:40:35.900
progression.

00:40:36.760 --> 00:40:44.643
And so the objective of this study was to
use quantitative CT metrics of airway,

00:40:44.643 --> 00:40:52.040
vascular and parenchymal findings on CTs
to predict future ILD development.

00:40:52.040 --> 00:40:54.960
And it was, it included two cohorts.

00:40:54.960 --> 00:40:59.789
There was a Vanderbilt cohort which was
first degree relatives of familial

00:40:59.789 --> 00:41:04.297
pulmonary fibrosis patients,
and then there was a Cornell cohort that

00:41:04.297 --> 00:41:06.680
was just incidentally identified ILA.

00:41:07.440 --> 00:41:10.840
And so they used this automated.

00:41:11.200 --> 00:41:13.431
I don't even know the right way to
pronounce it,

00:41:13.431 --> 00:41:15.480
but I've been calling it FLUIDDA in my
head.

00:41:16.200 --> 00:41:20.717
Quantitative CT analysis of the volume
and morphology of airways and pulmonary

00:41:20.717 --> 00:41:25.120
vasculature as well as parenchymal
density and texture. And in their cohort,

00:41:25.120 --> 00:41:30.241
So there were 8 ILD events in the
Vanderbilt cohort and had a median follow

00:41:30.241 --> 00:41:31.320
up of 38 months.

00:41:31.600 --> 00:41:36.075
And then in the Cornell cohort there were
7 ILD events with a median follow up of

00:41:36.075 --> 00:41:36.840
18 1/2 months.

00:41:36.840 --> 00:41:38.280
So not quite as long as follow up.

00:41:39.400 --> 00:41:44.460
And basically they found that there were
several different features and

00:41:44.460 --> 00:41:50.012
quantitative CT that were associated with
subsequently going on to develop ILD

00:41:50.012 --> 00:41:55.494
involving things like airway tortuosity,
wall area, radius, pulmonary vessel,

00:41:55.494 --> 00:41:56.760
fractal dimension.

00:41:56.760 --> 00:42:00.150
I'm sure Daniel's getting really excited
and was going to ask me all these

00:42:00.150 --> 00:42:02.320
questions that I can't answer about this
stuff.

00:42:02.320 --> 00:42:07.766
But basically the,
the key take away is that they did find

00:42:07.766 --> 00:42:14.412
11 candidate biomarkers that were
associated with predicting ILD or ILA

00:42:14.412 --> 00:42:15.519
progression.

00:42:15.760 --> 00:42:20.462
And then eight of these 11 showed
directional concordance across both

00:42:20.462 --> 00:42:21.000
cohorts.

00:42:21.000 --> 00:42:25.765
And so the idea is that, you know,
maybe we can use quantitative CT to help

00:42:25.765 --> 00:42:27.960
us risk stratify patients with ILA.

00:42:27.960 --> 00:42:29.280
And this is a really busy slide.

00:42:29.280 --> 00:42:32.360
Like you don't need to really pay too
much attention to it.

00:42:32.360 --> 00:42:39.280
It's just basically showing that they're,
these are like all the little things that

00:42:39.280 --> 00:42:45.789
the quantitative CT looked at and then
basically they identified 8 that showed

00:42:45.789 --> 00:42:48.920
the same direction as in both cohorts.

00:42:49.160 --> 00:42:51.200
So I think, you know, it's kind of,
it's really neat.

00:42:51.200 --> 00:42:55.792
Obviously,
I think we still have a ways to go with

00:42:55.792 --> 00:43:01.736
this stuff, but you know,
hopefully important tool for the future

00:43:01.736 --> 00:43:06.960
and I'll move along to quantitative CT in
general in ILD.

00:43:07.080 --> 00:43:12.789
So there was talk about quantitative CT
in ILA and then also in established ILD

00:43:12.789 --> 00:43:17.000
there was a lot of quantitative CT stuff
presented at ATS.

00:43:18.840 --> 00:43:21.609
So you know, current guidelines,
as you know,

00:43:21.609 --> 00:43:25.884
define progressive pulmonary fibrosis
using a combination of symptoms,

00:43:25.884 --> 00:43:30.280
lung function decline and then radiologic
evidence of progression on CT.

00:43:31.800 --> 00:43:36.543
The radiologic criterion relies on
qualitative visual assessment and we know

00:43:36.543 --> 00:43:40.979
there's lots of data that shows
interobserver agreement isn't great and

00:43:40.979 --> 00:43:43.320
also is insensitive to subtle changes.

00:43:43.320 --> 00:43:47.143
So hence QCT,
which as you know refers to this computer

00:43:47.143 --> 00:43:51.376
based analysis of CT can hopefully
provide us with objective,

00:43:51.376 --> 00:43:56.360
reproducible and a continuous measure of
disease extent and progression.

00:43:56.360 --> 00:43:57.400
So that's the premise.

00:43:57.400 --> 00:44:03.203
So sounds great,
and there are so many different QCT

00:44:03.203 --> 00:44:04.080
metrics.

00:44:04.080 --> 00:44:08.360
Here are some just to give you an idea
for people like myself that aren't QCT

00:44:08.360 --> 00:44:08.800
experts.

00:44:08.800 --> 00:44:14.534
So you can get a fibrosis score,
lung volume, ground glass extent,

00:44:14.534 --> 00:44:16.760
vessel related structures.

00:44:16.760 --> 00:44:23.621
And these different metrics have been
shown to be associated with different

00:44:23.621 --> 00:44:26.240
things prognostically in ILD.

00:44:26.360 --> 00:44:29.634
So for example,
an increasing fibrosis score has been

00:44:29.634 --> 00:44:34.000
shown to independently predict mortality
and progression free survival.

00:44:34.000 --> 00:44:41.245
So there's lots of data that shows that
we can use QCT to predict some of these

00:44:41.245 --> 00:44:43.600
important outcomes in ILD.

00:44:46.600 --> 00:44:52.411
And so this was a neat abstract that was
presented at ATS called revised PPF,

00:44:52.411 --> 00:44:58.298
which was a multi centre observational
study that the goal of the study was to

00:44:58.298 --> 00:45:02.545
determine whether earlier identification
of progression,

00:45:02.545 --> 00:45:08.580
could we use quantitative CT to provide
objective imaging biomarkers of fibrosis

00:45:08.580 --> 00:45:13.051
and severity of progression and leave
support to, you know,

00:45:13.051 --> 00:45:18.640
potentially intervening earlier or
monitoring these patients more closely.

00:45:19.920 --> 00:45:26.465
And so there were three cohorts,
3 cohorts in this study that included 509

00:45:26.465 --> 00:45:31.614
ILD patients and,
and eventually 267 of these patients met

00:45:31.614 --> 00:45:36.239
the ATS criteria for progressive
pulmonary fibrosis.

00:45:36.240 --> 00:45:42.551
They developed clinically defined
progressive pulmonary fibrosis and what

00:45:42.551 --> 00:45:49.375
they did in the study was they used this
QCT algorithm called Brainomix e-Lung

00:45:49.375 --> 00:45:53.640
and there were two biomarkers that they
measured.

00:45:53.640 --> 00:46:01.072
So one was this WRVS which stands for
weighted reticulovascular score and then

00:46:01.072 --> 00:46:06.341
the other one TDE,
which which stands for total disease

00:46:06.341 --> 00:46:07.000
extent.

00:46:09.800 --> 00:46:15.020
And what they found was that the e-Lung
was able to identify radiologic

00:46:15.020 --> 00:46:20.677
progression before the clinical PPF
diagnosis in the patients that eventually

00:46:20.677 --> 00:46:23.360
did meet that clinical PPF diagnosis.

00:46:23.360 --> 00:46:29.568
So for example, in the, you know,
first cohort it identified it in 78% of

00:46:29.568 --> 00:46:35.609
the patients before the clinical
diagnosis and in the Cornell cohort is

00:46:35.609 --> 00:46:39.720
83% and in the University of Chicago it
was 52%.

00:46:39.800 --> 00:46:43.200
And it was quite a significant lead time
before the clinical diagnosis.

00:46:43.200 --> 00:46:47.120
So you know,
anywhere from 8 to 28 months before.

00:46:47.400 --> 00:46:51.324
So you know,
really this quantitative CT algorithm was

00:46:51.324 --> 00:46:57.246
able to identify those patients who would
go on to develop the clinical definition

00:46:57.246 --> 00:47:03.240
of progressive pulmonary fibrosis well in
advance of us humans being able to do it.

00:47:03.240 --> 00:47:07.942
Essentially,
they also found that having a baseline

00:47:07.942 --> 00:47:14.996
WRVS score 50% or higher was predictive
of future PPF across all three of the

00:47:14.996 --> 00:47:15.720
cohorts.

00:47:19.200 --> 00:47:29.451
And they also were able to find that a
certain increase of WRVS or TDE on serial

00:47:29.451 --> 00:47:34.640
CTs was associated with higher mortality.

00:47:35.440 --> 00:47:40.920
So really the take home message here is
that quantitative CT was able to identify

00:47:40.920 --> 00:47:46.000
progression months before routine
clinical diagnosis and then also was able

00:47:46.000 --> 00:47:50.880
to identify those patients who are at
risk for future PPF and mortality.

00:47:50.880 --> 00:47:53.588
So, you know,
I thought that was kind of neat and I

00:47:53.588 --> 00:47:56.817
certainly see, you know,
once these types of metrics are more

00:47:56.817 --> 00:48:00.670
validated and ready for prime time,
how they could be valuable in our our

00:48:00.670 --> 00:48:01.400
clinical work.

00:48:03.480 --> 00:48:04.560
All right, perfect.

00:48:04.560 --> 00:48:08.600
So leaving some time for questions.

00:48:08.600 --> 00:48:10.640
So just to do a quick summary recap.

00:48:10.640 --> 00:48:14.760
So we have some new drugs hopefully
coming to Canada soon.

00:48:15.080 --> 00:48:19.054
I think it's really great that we might
have options when tolerability is an

00:48:19.054 --> 00:48:23.081
issue we can think about add on therapy,
there's new drugs and pathways being

00:48:23.081 --> 00:48:24.320
studied, which is great.

00:48:25.520 --> 00:48:29.799
There's a lot of interest in
identification of earlier disease and

00:48:29.799 --> 00:48:33.952
trying to do more advanced risk
stratification using things like

00:48:33.952 --> 00:48:39.317
biomarkers and really lots of excitement
around QCT to assist us in both diagnosis,

00:48:39.317 --> 00:48:42.639
but also risk stratification and
identification of,

00:48:42.639 --> 00:48:46.600
of progression and hopefully being able
to intervene earlier.

00:48:46.600 --> 00:48:49.501
And, you know,
really trying to bring it all back to our

00:48:49.501 --> 00:48:49.960
patients.

00:48:49.960 --> 00:48:54.146
I think that, you know,
it's really great to see some of these

00:48:54.146 --> 00:48:58.997
advances and what's on the horizon in
order for us to be able to provide

00:48:58.997 --> 00:49:02.520
comprehensive care for our patients
living with ILD.