RCS - PureTech Health PLC - PRTC: IPF Data Support Lung Function Stabilization

Puretech HealthAnnouncement

21/05/2025 07:00

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RNS Number : 4930J  PureTech Health PLC  21 May 2025

21 May 2025

PureTech Health plc

 

PureTech's Deupirfenidone (LYT-100) Demonstrates Strong and Durable Efficacy
as a Monotherapy with Favorable Tolerability in Phase 2b ELEVATE IPF Trial

 

Deupirfenidone 825 mg TID slowed lung function decline in people with
idiopathic pulmonary fibrosis (IPF) to the range expected of healthy older
adults over 6 months; new, preliminary open-label extension data support
durability of this treatment effect over at least 52 weeks

 

Deupirfenidone 825 mg TID demonstrated a statistically significant benefit
compared to placebo in delaying IPF progression

 

Detailed safety analysis underscores favorable tolerability profile for
deupirfenidone

 

PureTech plans to meet with FDA before end of Q3 2025, with the goal of
initiating a Phase 3 trial by year-end

 

PureTech Health plc (https://puretechhealth.com/) (Nasdaq: PRTC, LSE: PRTC)
("PureTech" or the "Company"), a clinical-stage biotherapeutics company
dedicated to changing the lives of patients with devastating diseases,
delivered a late-breaking, oral presentation at the 2025 American Thoracic
Society (ATS) International Conference in San Francisco. The presentation
provided further insights into the successful Phase 2b ELEVATE IPF trial
(https://news.puretechhealth.com/news-releases/news-release-details/puretechs-deupirfenidone-lyt-100-slowed-lung-function-decline)
of deupirfenidone (LYT-100), highlighting the strength and durability of
deupirfenidone's treatment effect through at least 52 weeks while maintaining
favorable tolerability in patients living with idiopathic pulmonary fibrosis
(IPF).

 

"The ELEVATE IPF trial is one of the most promising Phase 2 studies we've seen
in IPF in recent years," said Toby Maher, M.D., Ph.D., Professor of Medicine
and Director of Interstitial Lung Disease at Keck School of Medicine,
University of Southern California, Los Angeles, and lead investigator in the
ELEVATE IPF trial. "The ability for a monotherapy to reduce lung function
decline close to a level seen in healthy older adults, and to sustain that
effect over time without compromising tolerability, is not something we have
seen with currently available therapies. Deupirfenidone has the potential to
raise the bar for what patients and physicians can expect from IPF treatment."

 

Data presented from PureTech's global Phase 2b randomized, double-blind,
active- and placebo-controlled, dose-ranging ELEVATE IPF trial demonstrated
the potential for deupirfenidone to offer a differentiated treatment option
for patients with IPF. In the trial, patients treated with deupirfenidone 825
mg three times a day (TID) experienced a slower rate of lung function
decline,(1) as measured by Forced Vital Capacity (FVC), at 26 weeks versus
those who were treated with placebo (-21.5 mL vs. -112.5 mL, respectively;
p=0.02).(2) This statistically significant difference represents a robust
treatment effect versus placebo of 80.9% for deupirfenidone 825 mg TID as a
monotherapy. This result compares favorably against the rate of decline in FVC
observed in the trial among patients treated with pirfenidone 801 mg TID
versus placebo (-51.6 mL vs. -112.5 mL, respectively), which was consistent
with previously reported pirfenidone clinical trial data(3) and represents a
treatment effect of 54.1%. Taken together, these results indicate that the
treatment effect with deupirfenidone 825 mg TID was approximately 50% greater
than that of pirfenidone 801 mg TID, based on their respective reductions in
lung function decline versus placebo (80.9% vs. 54.1%).

 

In addition to these findings, deupirfenidone 825 mg TID also demonstrated a
statistically significant benefit in delaying time to IPF progression(4)
compared to placebo (hazard ratio = 0.439; p=0.0023), further supporting the
clinical relevance of the treatment effect.

 

Importantly, the rate of FVC decline observed over 26 weeks with
deupirfenidone 825 mg TID (-21.5 mL) was similar to the expected natural
decline in lung function in healthy older adults (approximately -15.0 mL to
-25.0 mL).(5,6) Furthermore, preliminary data from the ongoing open-label
extension (OLE) study suggest that this treatment effect is durable out to at
least 52 weeks. As of May 9, 2025, a total of 101 patients had received at
least 52 weeks of treatment with deupirfenidone. Those in the deupirfenidone
825 mg TID arm experienced a decline in FVC of -32.8 mL over the 52-week
period,(7) which is similar to the expected natural decline in lung function
in healthy older adults over one year (approximately -30.0 mL to -50.0 mL).(6)
These new data provide additional support for the durability of the treatment
effect observed with this dose and reinforce its potential to stabilize lung
function decline over time, while maintaining favorable safety and
tolerability. Additional details from the ongoing OLE are expected to be
shared in a future scientific forum.

 

These results are further supported by preliminary pharmacokinetic (PK) data,
which underscore the differentiated profile of deupirfenidone. Compared to
pirfenidone 801 mg TID, deupirfenidone 825 mg TID resulted in an approximately
50% increase in drug exposure. Notably, the dramatically increased drug
exposure did not result in an increase in tolerability challenges, suggesting
that the deuterated structure of deupirfenidone may overcome the dose-limiting
adverse events associated with pirfenidone. PureTech believes these PK results
are consistent with the enhanced efficacy and favorable tolerability seen with
deupirfenidone 825 mg TID in the trial.

 

"The IPF community has long needed therapies that can provide meaningful
efficacy without compromising tolerability," said Bharatt Chowrira, Ph.D.,
J.D., Chief Executive Officer of PureTech. "Data from our Phase 2b trial and
open-label extension study suggest that deupirfenidone may slow lung function
decline in a way that more closely mirrors the natural aging process, and that
this effect is durable. These data are quite remarkable and - to our knowledge
- this level of efficacy has not been observed with other monotherapies. These
findings further support our belief that deupirfenidone may offer a
substantially differentiated treatment option for people living with IPF and
support its potential to become a new standard of care."

 

Deupirfenidone was well tolerated at both doses studied. Safety analyses
included identification of the 16 most common treatment-emergent adverse
events (TEAEs), defined as occurring in more than 5% of participants in at
least one treatment group, and characterized the arm with the highest relative
incidence of each of these 16 TEAEs. The pirfenidone 801 mg treatment group
had the highest relative incidence for 9 of these TEAEs, followed by
deupirfenidone 825 mg (5), placebo (2), and deupirfenidone 550 mg (0).

 

"The results of the ELEVATE IPF trial demonstrate the potential for
deupirfenidone to address the persistent suboptimal efficacy offered by
current standard-of-care treatments for IPF, without sacrificing
tolerability," Camilla Graham, M.D., M.P.H., Senior Vice President of Medical
Affairs at PureTech. "We are excited to continue development of deupirfenidone
to meaningfully improve the lives of patients living with IPF."

 

PureTech is targeting a meeting with the U.S. Food and Drug Administration by
the end of the third quarter of 2025 to discuss the results of the Phase 2b
trial and align on a potential registrational pathway, with the goal of
initiating a Phase 3 trial by the end of 2025. PureTech anticipates providing
further guidance later this year following the finalization of the trial
design and FDA interactions.

 

About the ELEVATE IPF Trial

The Phase 2b ELEVATE IPF trial was a global, randomized, double-blind, active-
and placebo-controlled, dose-ranging trial designed to evaluate the efficacy,
tolerability, safety and dosing regimen of deupirfenidone (LYT-100) in
patients with IPF compared to placebo. 257 participants were randomized in a
ratio of 1:1:1:1 to receive either 550 mg of deupirfenidone, 825 mg of
deupirfenidone, 801 mg pirfenidone or placebo three times a day (TID) for 26
weeks. Participants who completed the trial had the option to enroll in an
open-label extension, which is ongoing.

 

The primary endpoint of the trial was the rate of decline in Forced Vital
Capacity (FVC) for the combined deupirfenidone arms versus placebo over the
26-week treatment period. FVC is a measure of the maximum amount of air (in
mL) that an individual can forcibly exhale after fully inhaling. It is a
standard measurement in clinical trials for IPF and is used to assess disease
progression as well as to predict mortality.

 

A prespecified Bayesian analysis was utilized to assess the primary endpoint
and provided a posterior probability, which is the probability of superior
efficacy for deupirfenidone compared to placebo. This also allowed for
augmentation of the placebo arm with placebo data from historical IPF trials.
This approach enabled a more patient-centric clinical trial design by
minimizing the number of trial participants exposed to placebo - a key
consideration since IPF is progressive and fatal - while delivering a robust,
placebo-controlled dataset.

 

About Deupirfenidone (LYT-100)

Deupirfenidone (LYT-100) is an investigational therapy in development as a
potential new standard of care (SOC) for the treatment of idiopathic pulmonary
fibrosis (IPF). It is a deuterated form of pirfenidone, which - along with
nintedanib - is one of the two FDA-approved treatments for IPF. Despite
achieving blockbuster status, the current SOC treatments only modestly slow
lung function decline, with tolerability limiting the ability to achieve
higher doses. This results in suboptimal efficacy, reduced patient uptake, and
poor adherence - all due to a tolerability ceiling that prevents dosing levels
that could significantly improve patient outcomes.

 

Deupirfenidone may overcome these limitations. In the global Phase 2b ELEVATE
IPF trial, deupirfenidone demonstrated the potential to stabilize lung
function decline over at least 26 weeks as a monotherapy while maintaining
safety and tolerability - a result not previously achieved by other
investigational or marketed IPF therapies to the Company's knowledge. These
findings support the potential for deupirfenidone to offer a meaningful
advance for patients living with this progressive and life-limiting disease.
Beyond IPF, deupirfenidone may also address multiple underserved fibrotic
diseases, including progressive fibrosing interstitial lung diseases and other
fibrotic conditions.

 

About Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic Pulmonary Fibrosis (IPF) is a rare, progressive and fatal lung
disease characterized by irreversible scarring of lung tissue. Median survival
following diagnosis is estimated to be two to five years.(8) IPF affects more
than 230,000 people across the United States and EU5 (France, Germany, Italy,
Spain, and the United Kingdom).(9)

 

Although two therapies are approved to treat IPF, their use remains limited,
and nearly three out of four people with IPF in the United States have never
received either treatment.(10) There remains a significant need for therapies
that can more effectively slow or stabilize disease progression, while
maintaining favorable tolerability, to improve outcomes for people living with
IPF.

 

About PureTech Health

PureTech is a clinical-stage biotherapeutics company dedicated to giving life
to new classes of medicine to change the lives of patients with devastating
diseases. The Company has created a broad and deep portfolio through its
experienced research and development team and its extensive network of
scientists, clinicians, and industry leaders that is being advanced both
internally and through its Founded Entities. PureTech's R&D engine has
resulted in the development of 29 therapeutics and therapeutic candidates,
including three that have been approved by the U.S. Food and Drug
Administration. A number of these programs are being advanced by PureTech or
its Founded Entities in various indications and stages of clinical
development, including registration-enabling studies. All of the underlying
programs and platforms that resulted in this portfolio of therapeutic
candidates were initially identified or discovered and then advanced by the
PureTech team through key validation points.

 

For more information, visit www.puretechhealth.com
(http://www.puretechhealth.com) or connect with us on X (formerly Twitter)
@puretechh.

 

Cautionary Note Regarding Forward-Looking Statements

This press release contains statements that are or may be forward-looking
statements within the meaning of the Private Securities Litigation Reform Act
of 1995. All statements contained in this press release that do not relate to
matters of historical fact should be considered forward-looking statements,
including without limitation those related to the deupirfenidone (LYT-100)
development program and development plans, its potential benefits to patients,
plans for discussions with regulatory authorities, the further development of
the program, future presentation of additional data from the trial and our
future prospects, developments and strategies. The forward-looking statements
are based on current expectations and are subject to known and unknown risks,
uncertainties and other important factors that could cause actual results,
performance and achievements to differ materially from current expectations,
including, but not limited to, those risks, uncertainties and other important
factors described under the caption "Risk Factors" in our Annual Report on
Form 20-F for the year ended December 31, 2024, filed with the SEC and in our
other regulatory filings. These forward-looking statements are based on
assumptions regarding the present and future business strategies of the
Company and the environment in which it will operate in the future. Each
forward-looking statement speaks only as at the date of this press release.
Except as required by law and regulatory requirements, we disclaim any
obligation to update or revise these forward-looking statements, whether as a
result of new information, future events or otherwise.

 

References

(1) Efficacy analysis used a random coefficient regression model with absolute
FVC including baseline as response variable and week, treatment and
interaction between week and treatment as fixed effect. The analysis was
performed based on the predefined Full Analysis Set.

2 All p values are two-sided and have not been corrected for multiplicity.

3 Roche. (2014). Esbriet® (pirfenidone) prescribing information. U.S. Food
and Drug Administration.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022535s000lbl.pdf
(https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022535s000lbl.pdf)

4 IPF progression was defined as a ≥5% decline in FVCpp or death.

5 FVC decline at 6 months was estimated assuming linear decline over time.

6 Valenzuela, C., Bonella, F., Moor, C., Weimann, G., Miede, C., Stowasser,
S., & Maher, T. (2024, September). Decline in forced vital capacity (FVC)
in subjects with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary
fibrosis (PPF) compared with healthy references [Poster presentation].
European Respiratory Society International Congress, Vienna, Austria; and
Luoto, J., Pihlsgård, M., Wollmer, P., & Elmståhl, S. (2019). Relative
and absolute lung function change in a general population aged 60-102 years.
European Respiratory Journal, 53(3), 1701812.
https://doi.org/10.1183/13993003.01812-2017
(https://doi.org/10.1183/13993003.01812-2017)

7 Analysis conducted using the same methodology to assess rate of decline in
FVC at 26 weeks from the double-blind portion of the trial (see reference 1)

8 Fisher, M., Nathan, S. D., Hill, C., Marshall, J., Dejonckheere, F.,
Thuresson, P., & Maher, T. M. (2017). Predicting life expectancy for
pirfenidone in idiopathic pulmonary fibrosis. Journal of Managed Care &
Specialty Pharmacy, 23(3-b Suppl), S17-S24.
https://doi.org/10.18553/jmcp.2017.23.3-b.s17
(https://doi.org/10.18553/jmcp.2017.23.3-b.s17)

9 GlobalData. (n.d.). Epidemiology and market size search: EU5 = United
Kingdom, France, Germany, Italy, and Spain. GlobalData Healthcare Database.

10 Dempsey, T. M., Payne, S., Sangaralingham, L., Yao, X., Shah, N. D., &
Limper, A. H. (2021). Adoption of the antifibrotic medications pirfenidone and
nintedanib for patients with idiopathic pulmonary fibrosis. Annals of the
American Thoracic Society, 18(7), 1121-1128.

 

Contact:

PureTech

Public Relations

publicrelations@puretechhealth.com (mailto:publicrelations@puretechhealth.com)

Investor Relations

ir@puretechhealth.com (mailto:ir@puretechhealth.com)

UK/EU Media

Ben Atwell, Rob Winder

+44 (0) 20 3727 1000

puretech@fticonsulting.com (mailto:puretech@fticonsulting.com)
 

US Media

Justin Chen

+1 609 578 7230

jchen@tenbridgecommunications.com (mailto:jchen@tenbridgecommunications.com)

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