High-dose LTI-03 (5 mg BID), a Caveolin-1
related peptide, reduced expression of multiple profibrotic
proteins in both pathological basal-like cells and fibroblasts and
decreased the expression of a biomarker indicative of epithelial
health and lung function decline, suggesting potential therapeutic
effect
Positive trend observed in seven out of eight
IPF biomarkers in Cohort 2, with four biomarkers statistically
significant in the combined Cohort 1 and Cohort 2 data set, and
dose dependent movement of five biomarkers compared to low dose
LTI-03 indicative of active LTI-03 pharmacodynamics
High-dose LTI-03 was well-tolerated, with no
safety signals observed
Planning is underway for a Phase 2 clinical
trial
Company to host conference call today at
8:30 am ET
WALTHAM,
Mass., Nov. 13, 2024 /PRNewswire/ -- Aileron
Therapeutics, Inc. ("Aileron") (NASDAQ: ALRN), a biopharmaceutical
company advancing a novel pipeline of first-in-class medicines to
address significant unmet medical needs in orphan pulmonary and
fibrosis indications, today announced positive topline data from
Cohort 2 of its Phase 1b clinical
trial evaluating the safety and tolerability of inhaled LTI-03 in
patients diagnosed with idiopathic pulmonary fibrosis (IPF). LTI-03
is a novel, Caveolin-1-related peptide that modulates both
pro-fibrotic activity and sustain critical alveolar epithelial
cells.
Following inhaled administration of high dose
LTI-03 (5 mg BID), a positive trend was observed in seven out of
eight biomarkers, with evidence of reduced expression among
profibrotic proteins produced by basal-like cells and fibroblasts
that contribute to the progression of IPF, including data from four
biomarkers that were statistically significant in the combined data
set of Cohort 1 and Cohort 2, and data from five biomarkers that
showed dose dependence relative to the data from those biomarkers
in Cohort 1. Overall, the collective findings from this Phase
1b clinical trial provide the Company
with strong confidence that LTI-03 has the potential to improve
lung function and reverse the course of IPF.
"We are extremely pleased with the results
achieved by high dose LTI-03, including measuring statistical
significance in three biomarkers in Cohort 2, with the combined
data sets showing even stronger results, with four statistically
significant biomarkers," said Brian
Windsor, Ph.D., President and Chief Executive Officer of
Aileron. "Additionally, we saw dose dependent effects in five
biomarkers which provides evidence of active LTI-03
pharmacodynamics. We believe that this data, including the 5%
decrease in surfactant protein D, a biomarker for epithelial cell
health, at 14 days of treatment, reinforces LTI-03's potential for
disease stabilization or even reversal. We look forward to
evaluating LTI-03 in a Phase 2 study."
"I am delighted with the Cohort 2 data as it
confirms previous results obtained with LTI-03 in cell experiments,
animal studies and ex-vivo studies employing human IPF high
precision cut lung slices. In these studies, the evaluated
biomarkers were found to be downregulated by LTI-03. These
observations have now been reproduced in IPF patients upon
inhalative application of LTI-03 vs placebo," said Prof.
Andreas Gunther, M.D., Head of the
Center for Interstitial and Rare Lung Diseases of the Justus Liebig
University in Giessen, Germany.
"Moreover, the profile of the statistically significant changes in
the biomarkers in response to LTI-03 treatment also suggests that
LTI-03 may not only act on fibroblasts, but also on epithelial
cells, which would represent a novel therapeutic principle in the
IPF treatment landscape. IPF is a devastating disease with
worsening quality of life over time, and LTI-03 has the potential
to meaningfully impact the current treatment paradigm. I look
forward to further evaluating LTI-03´s potential in a Phase 2
study."
Summary of Cohort 2 Analysis
Twelve patients were enrolled in Cohort 2 of the
ongoing Phase 1b clinical trial,
three in the placebo arm and nine in the active arm. Patients had a
bronchoscopy at baseline, received a high dose of LTI-03 (5mg BID)
twice a day for 14 days, followed by a bronchoscopy on day 14 and
seven days of post-treatment follow-up. Cohort 2 findings
include:
- Reduced expression of multiple profibrotic proteins active
in both pathologic basal-like cells and fibroblasts, with four
biomarkers (IL-11, CXCL7, TSLP and GAL-7) showing statistically
significant decreases in the combined data set supporting the
potential of LTI-03 to reduce fibrosis, inflammation and associated
functional changes in the lung.
- Dose dependent trends were observed in five biomarkers,
including COL1A1, CXCL7, TSLP, GAL-7, and Surfactant protein D
(SPD) which provide evidence of active LTI-03
pharmacodynamics.
- SPD, an indicator of epithelial cell health that is
significantly linked to decline in lung function, decreased by 5%
in Cohort 2 at 14 days of treatment, while current standard of care
for IPF reduced SPD by 4% at 12-weeks in precedent trials1,
2.
- LTI-03 did not induce inflammation in peripheral blood
mononuclear cells (PBMCs) in either Cohort, measured by pAKT, a
safety marker for inflammation in this trial.
- LTI-03 was generally well-tolerated, and there were no
drug-related adverse events that resulted in a discontinuation of
the trial.
Conference Call Information
Aileron will host a conference call on
Wednesday, November 13th
at 8:30 am ET to discuss the topline
results from Cohort 2 of the Phase 1b
clinical trial of LTI-03 in IPF. To access the call, please dial +1
646-876-9923 (domestic) or +44 330-088-5830 (international) and
reference meeting ID: 951-8768-4226 when prompted by the operator.
A live webcast of the event can be accessed
at https://investors.aileronrx.com/events-presentations/investor-events.
A replay of the webcast will be available following the completion
of the event.
About the Phase 1b Clinical Trial of LTI-03
The Phase 1b
clinical trial of LTI-03 is a randomized, double-blind, placebo
controlled, multi-center, dose escalation study in patients
recently diagnosed with IPF that have not received prior treatment
with anti-fibrotic agents for at least two months (NCT05954988).
Eligible patients are randomly assigned (3:1) to receive one of two
doses of LTI-03 or placebo. The primary objective of the study is
to investigate the safety and tolerability of LTI-03 in patients
with IPF after treatment for 14 consecutive days, with multiple
biomarker concentration as exploratory endpoints.
About IPF
IPF is a chronic lung disease characterized
by progressive tissue scarring that prevents proper lung function.
It is a progressive, fatal, age-associated lung disease affecting
approximately 100,000 people in the
United States3. IPF typically presents in adults
65 or older and is usually fatal within two to five years after
diagnosis4.
About LTI-03 and Caveolin-1 (Cav1)
LTI-03 is a seven amino acid peptide, the
sequence of which is derived from the caveolin scaffolding domain
(CSD), an important binding region of the Cav1 protein. Cav1
normally serves a critical function in the prevention of fibrosis
by maintaining a balance between pathways that both initiate and
arrest lung repair and cell movement. Through the CSD, caveolin
interacts with a large number of signaling molecules, all of which
possess a caveolin binding domain region. Cav1 expression is
decreased in IPF lung tissues and has been demonstrated to decrease
during the fibrotic phase of bleomycin, or BLM, lung injury in
mice. Restoring the balance of important biological signals in the
lung may not only slow lung function decline but could also restore
healthy lung function through the protection of healthy epithelial
cells.
About Aileron Therapeutics
Aileron Therapeutics is a biopharmaceutical
company advancing a novel pipeline of first-in-class medicines to
address significant unmet medical needs in orphan pulmonary and
fibrosis indications. Aileron's lead product candidate, LTI-03, is
a novel, synthetic peptide with a dual mechanism targeting alveolar
epithelial cell survival as well as inhibition of profibrotic
signaling. LTI-03 completed a Phase 1b clinical trial for the treatment of idiopathic
pulmonary fibrosis. Aileron's second product candidate, LTI-01, is
a proenzyme that has completed Phase 1b and Phase 2a clinical trials for the treatment
of loculated pleural effusions. LTI-01 has received Orphan Drug
Designation in the US and EU and Fast Track Designation in the
US.
References
1Jenkins RG, Cottin V, Nishioka Y, et
al. Effects of nintedanib on circulating biomarkers of idiopathic
pulmonary fibrosis. ERJ Open Res 2024; in press
(https://doi.org/10.1183/23120541.00558-2023).
2The biomarker data regarding change in SPD in this
trial and the data from the INMARK trial of nintedanib compares two
clinical trials with different trial designs, patient enrollment
criteria and treatment regimens. In addition, the applicable
measurements were observed over different time periods. As a
result, the data from these trials may not be directly
comparable.
3Pergolizzi, Jr., J., LeQuang, J., Varrassi, M., Breve,
F., Magnusson, P., Varrassi, G., (2023). What Do We Need to Know
About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative
Review and Update. Springer Nature, Published online 2023 Jan 24.
Doi: 10.1007/s12325-022-02395-9.
4Nathan et al. "Long-term Course and Prognosis of
Idiopathic Pulmonary Fibrosis in the New Millennium". Chest Journal
Volume 140, ISSUE 1, P221-229, July
2011.
Forward-Looking Statements
This press release may contain forward-looking
statements of Aileron Therapeutics, Inc. ("Aileron", the "Company",
"we", "our" or "us") within the meaning of the Private Securities
Litigation Reform Act of 1995, including statements with respect
to: the timing and expectation of a Phase 2 trial of LTI-03; future
expectations, plans and prospects for the Company, the sufficiency
of the Company's cash resources; and the potential commercial
opportunity of LTI-03 and LTI-01. We use words such as
"anticipate," "believe," "estimate," "expect," "hope," "intend,"
"may," "plan," "predict," "project," "target," "potential,"
"would," "can," "could," "should," "continue," and other words and
terms of similar meaning to help identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Actual results may differ materially from
those indicated by such forward-looking statements as a result of
various important factors, including risks and uncertainties
related to changes in applicable laws or regulations, the
possibility that the Company may be adversely affected by other
economic, business, and/or competitive factors, including risks
inherent in pharmaceutical research and development, such as:
adverse results in the Company's drug discovery, preclinical and
clinical development activities, the risk that the results of
preclinical studies and early clinical trials may not be replicated
in later clinical trials, including in a Phase 2 trial of LTI-03,
or that partial results of a trial will be indicative of the full
results of the trial, the Company's ability to enroll patients in
its clinical trials, and the risk that any of its clinical trials
may not commence, continue or be completed on time, or at all;
decisions made by the U.S. Food and Drug Administration and other
regulatory authorities, investigational review boards at clinical
trial sites and publication review bodies with respect to our
development candidates; our ability to obtain, maintain and enforce
intellectual property rights for our platform and development
candidates; competition; uncertainties as to the sufficiency of the
Company's cash resources to fund its planned activities for the
periods anticipated and the Company's ability to manage unplanned
cash requirements; and general economic and market conditions; as
well as the risks and uncertainties discussed in the "Risk Factors"
section of the Company's Annual Report on Form 10-K for the year
ended December 31, 2023 and the
Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, which are on file with the United
States Securities and Exchange Commission (the "SEC"), and in
subsequent filings that the Company files with the SEC. These
forward-looking statements should not be relied upon as
representing the Company's view as of any date subsequent to the
date of this press release, and we expressly disclaim any
obligation to update any forward-looking statements, whether as a
result of new information, future events or otherwise, except as
required by law.
Investor Relations & Media
Contact:
Argot Partners
aileron@argotpartners.com
212-600-1902
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SOURCE Aileron Therapeutics, Inc.