PTI-801 Moving to 14 Day Proof of Concept Study
in CF Subjects on Orkambi®PTI-428 Continues to Enroll 28 Day Proof
of Concept Study in CF Subjects on Orkambi®PTI-808 Investigational
New Drug Application Now Active; Phase 1 Study in Healthy
Volunteers Initiated
Proteostasis Therapeutics, Inc. (NASDAQ:PTI), a biopharmaceutical
company developing small molecule therapeutics to treat diseases
caused by dysfunctional protein processing such as cystic fibrosis
(CF), announced updates across the Company’s later stage
development programs in CF, including PTI-428, a cystic fibrosis
transmembrane conductance regulator (CFTR) amplifier, PTI-801, a
new generation CFTR corrector, and PTI-808, a CFTR potentiator.
Proteostasis announced that it has completed
dosing of 19 patients as part of the ongoing Phase 1/2 study
designed to evaluate the safety and pharmacokinetics of PTI-428,
the Company’s CFTR amplifier. PTI-428 was administered together
with background Orkambi® (lumacaftor/ivacaftor) or as the only CFTR
modulator therapy in CF subjects over a 14-day period (7-day dosing
followed by 7-day follow-up period). The trial met its primary
safety and pharmacokinetic endpoints, confirming PTI-428’s safety,
tolerability and lack of clinically meaningful drug-drug
interaction with ivacaftor and lumacaftor.
“Preliminary data suggests that PTI-428
continues to demonstrate a favorable safety and pharmacokinetic
profile, which has enabled the initiation of Phase 2, enrolling CF
subjects on background Orkambi® taking PTI-428 or placebo for 28
days,” said Meenu Chhabra, President and CEO of Proteostasis
Therapeutics. “We continue to make meaningful progress with all
three components of our proprietary triple combination: with
the support of US and EU patient advocacy groups for the PTI-801
protocol, we are eligible to begin screening and enrolling CF
subjects on background Orkambi® and 40 clinical sites in the US,
Canada and EU have been identified or are in process of activation;
enrollment continues in our 28-day study of PTI-428 across 14
active clinical sites in the US, with activation of another 23
sites in both the US and EU in process; and we have initiated a
Phase 1 study of PTI-808 in healthy volunteers.”
In the Phase 1 portion of the PTI-428 study, 11
subjects in the Orkambi® cohort and eight in the PTI-428
monotherapy cohort were enrolled, with each group enrolling 2
placebo subjects. All adverse events (AEs) were mild or
moderate and none occurred in more than one subject. There
were no hematology-related adverse events and no serious adverse
events (SAEs) reported. Safety endpoints evaluated included
lung function as measured by forced expiratory volume in one second
(FEV1), although the study was not designed to show a statistically
significant difference. In the subjects who received PTI-428
in addition to their background Orkambi, there was no significant
improvement of FEV1 compared to placebo, although there was a
numerical increase in FEV1 at day 7. Measurements of sweat
chloride and mRNA in nasal mucosa were used as exploratory
biomarkers but the changes were not significant nor correlated with
lung function changes.
Ms. Chhabra added, “While confirming the safety
of PTI-428, the phase 1 portion of this study was not expected to
demonstrate efficacy over a 7-day dosing period, as PTI-428, as a
CFTR amplifier, is designed to deliver substrate to correctors and
was investigated in combination with Orkambi®, whose signal of
efficacy required a 28-day study. As a result, we look
forward to generating data in our 28-day proof-of-concept study to
begin understanding the activity profile of PTI-428.”
Proteostasis is enrolling patients in the Phase 2 safety and
efficacy portion of the study, which explores PTI-428 dosed over a
28-day period, and preliminary data is expected in Q4 2017.
Po-Shun Lee, M.D., Executive Vice President,
Chief Medical Officer, added: “This is a very exciting time for the
CF community, with the potential of next generation CFTR modulator
therapies and combinations just beginning to emerge inclusive of
doublets, triplets and quadruplets. We believe that PTI-428,
PTI-801 and PTI-808 have the potential to play a pivotal role in
emerging next generation therapies as proprietary combinations and
as add-ons to the evolving standard of care. In fact, recent
clinical data published with triple combinations of CFTR modulators
confirms that in vitro assays have high translational value
correlating with improvements in lung function beyond what had been
observed to date. This continues to reinforce the correlation
between in vitro chloride transport and FEV1 and further suggests a
ceiling on lung function improvement has not yet been
established.”
Proteostasis also announced today that the
protocol for the CF portion of its Phase 1/2 study of PTI-801, a
new generation CFTR corrector with Fast Track designation from the
FDA, has been endorsed by the Cystic Fibrosis Foundation
Therapeutics Development Network (TDN) Protocol Review Committee
and the European Cystic Fibrosis Society Clinical Trial Network
(CTN). Screening of CF subjects for 14-day dosing in this
study is in the process of being initiated, with initial data
expected in Q4 2017. A total of 52 healthy volunteers have
participated and completed the study. All AEs in the healthy
volunteer portion of the study that have been reported to date were
of mild or moderate intensity. No AEs were reported in more than
one subject and no SAEs were reported. PTI-801 was found to
be generally well tolerated. Preliminary PK assessments indicated
that PTI-801 was well absorbed following single and multiple oral
administrations, and suggest that it could be suitable for once
daily dosing. In vitro studies have shown that the addition of
PTI-801 to either a lumacaftor/ivacaftor or tezacaftor/ivacaftor
combination increased the effect of both combinations by
approximately three-fold.
The Company also announced today that its
Investigational New Drug application with the U.S. Food and Drug
Administration for PTI-808, a CFTR potentiator, is now active and
that the Company has initiated a Phase 1 study in healthy
volunteers. If positive efficacy results are achieved in the
PTI-428 and PTI-801 programs, Proteostasis intends to initiate a
triple combination study at the end of 2017 with all three agents
(also known as PTI-NC-733). The study will explore different doses
of PTI-808 with fixed dose combination of PTI-428 and PTI-801 in an
F508del homozygous population who are not taking Orkambi®.
About Proteostasis Therapeutics,
Inc.
Proteostasis Therapeutics, Inc. is a
biopharmaceutical company dedicated to the discovery of
groundbreaking therapies to treat diseases caused by dysfunctional
protein processing, such as cystic fibrosis (CF). Headquartered in
Cambridge, MA, the Proteostasis Therapeutics team focuses on
identifying therapies that restore protein function. In addition to
its multiple programs in cystic fibrosis, Proteostasis Therapeutics
has formed a collaboration with Astellas Pharma, Inc. to research
and identify therapies targeting the Unfolded Protein Response
(UPR) pathway. For more information, visit
www.proteostasis.com.
Safe Harbor
To the extent that statements in this release
are not historical facts, they are forward-looking statements
reflecting the current beliefs and expectations of management made
pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. Words such as “aim,” “may,”
“will,” “expect,” “anticipate,” “estimate,” “intend,” and similar
expressions (as well as other words or expressions referencing
future events, conditions or circumstances) are intended to
identify forward-looking statements. Examples of
forward-looking statements made in this release include, without
limitation, statements regarding the expected timing of the
initiation of, patient enrollment in, data from, and our completion
of, our clinical studies and cohorts for PTI-428, PTI-801, PTI-808
and our triple combination therapy candidate,
PTI-NC-733. Forward-looking statements made in this
release involve substantial risks and uncertainties that could
cause actual results to differ materially from those expressed or
implied by the forward-looking statements, and we therefore cannot
assure you that our plans, intentions, expectations or strategies
will be attained or achieved. Such risks and uncertainties
include, without limitation, the possibility final or future
results from our drug candidate trials (including, without
limitation, longer duration studies) do not achieve positive
results or are materially and negatively different from or not
indicative of the preliminary results reported in this release,
(noting that these results are on a small number of patients and
small data set), uncertainties inherent in the execution and
completion of clinical trials (including, without limitation, the
possibility FDA requires us to run cohorts sequentially or conduct
additional cohorts or pre-clinical or clinical studies), in the
enrollment of CF patients in our clinical trials, in the timing of
availability of trial data, in the results of the clinical trials,
in possible adverse events from our trials, in the actions of
regulatory agencies, in endorsement, if any, by therapeutic
development arms of CF patient advocacy groups, and those set forth
in our Annual Report on Form 10-K for the year ended December 31,
2016, and our other SEC filings. We assume no obligation to
update or revise any forward-looking statements, whether as a
result of new information, future events or otherwise.
CONTACTS:
Investors:
David Pitts
Argot Partners
212.600.1902
david@argotpartners.com
Media:
Eliza Schleifstein
Argot Partners
973.361.1546
eliza@argotpartners.com
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