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), today announced preliminary data from the Multiple Ascending
Dose (MAD) cohort of its Phase 1 trial designed to evaluate the
safety and pharmacokinetics of PTI-428 in CF subjects.
PTI-428 is the Company’s cystic fibrosis transmembrane
conductance regulator (CFTR) amplifier.
“To date, we have dosed 15 subjects in two
patient populations, those who are taking Orkambi® and those not
taking CFTR modulator based therapies. We have increased the size
of both cohorts, enrolling beyond our initial targets in the former
cohort, with the latter on its way to over-enrollment, reflecting
investigator enthusiasm,” said Meenu Chhabra, president and chief
executive officer of Proteostasis Therapeutics. “Based on safety
and PK data from 12 patients in the two CF populations, the Safety
Review Committee (SRC) has approved initiation of our
longer-duration cohort of PTI-428 and the first patient has already
been screened. This Phase 2 portion of the study is expected to
inform us on a dose level for the triple combination
proof-of-concept study combining our three CFTR modulators,
PTI-428, PTI-801 and PTI-808.”
Ms. Chhabra continued: “PTI-428 is unique among
CFTR modulators, in that in vitro studies suggest activity across
CFTR genotypes, enabling a potential treatment paradigm where
therapy for the majority of CF patients could be based on
combinations anchored by PTI-428. We look forward to
continuing to follow and enroll patients in our PTI-428 studies,
and to announcing additional data from this trial in
July.”
For the cohort with background Orkambi® therapy,
a total of ten patients with CF have been dosed to date.
Safety and PK data from the first eight subjects who have completed
dosing and follow-up were evaluated by the SRC. Primary endpoints
of the study were safety, tolerability and pharmacokinetics
(PK). Patients were randomized to receive 100 mg PTI-428 or
placebo for seven days in addition to their background Orkambi®
therapy. PTI-428 was generally well tolerated, with no
serious adverse events and no adverse events leading to
discontinuation observed, and adverse events observed in subjects
were mild (two) or moderate (one), and were deemed unrelated to
study therapy. Preliminary data confirmed the PTI-428 PK profile to
be comparable to that achieved in healthy volunteers and showed a
lack of impact on Orkambi® exposure levels, including both
ivacaftor and lumacaftor, suggesting no clinically significant
drug-drug interaction. Notably, peak concentration achieved
approached EC90 for PTI-428.
Safety endpoints included forced expiratory
volume in one second (FEV1) and exploratory endpoints included
changes in sweat chloride (SC) and CFTR mRNA. Preliminary analysis
of changes in respiratory function for those patients with complete
lung function data over the study period indicates a positive trend
from baseline to the end of the 7-day dosing period, as measured by
FEV1, and return to baseline levels at the end of the 7-day follow
up period. The overall changes in lung function during the
treatment interval favored the group that received PTI-428 versus
placebo, although such changes were not statistically significant,
as the study was not designed to confirm difference from
placebo. Preliminary sweat chloride data suggest that PTI-428
modulates CFTR activity. The alteration in SC is consistent with
published data on lumacaftor and tezacaftor, where changes in SC
levels did not correlate with FEV1 improvement. With a
limited dataset, a correlation has not been observed between CFTR
mRNA and FEV1. Further analysis of the study, including
follow up on all patients enrolled in this cohort, is expected to
be reported in July.
For the cohort of CF patients not currently on
CFTR modulator therapy, subjects received PTI-428, or placebo, as
their sole CFTR modulator therapy for seven days. While this
cohort remains blinded, of the five patients enrolled to date, four
were evaluated by the SRC for safety and tolerability, and
treatment was found to be generally well tolerated with no
treatment related adverse events observed. Five adverse
events observed so far were all mild. Further analysis from the
PTI-428-only cohort, including follow up on all patients enrolled,
is also expected to be reported in July.
A separate study with a third patient population
is initiating enrollment of CF patients who will receive PTI-428 or
placebo in addition to Kalydeco® as background therapy for 14 days.
Proteostasis expects to announce preliminary results from this
study during the third quarter.
PTI-428 Data Support Progression into Phase 2, 28-day
Dosing Cohort, Progressing to Triple Combination
(PTI-NC-733)After a washout period, patients on Orkambi®
background therapy who were enrolled in the 7-day dosing MAD cohort
are eligible to enroll in the Phase 2 portion of the PTI-428 study,
a 28-day dosing cohort. Upon review of the safety data from
the MAD cohort in CF subjects on background Orkambi® therapy, the
SRC has approved initiation of this next stage of clinical
development with PTI-428. The Company has initiated screening
of patients for the 28-day study and plans to report safety and
efficacy data from this cohort in Q4 of 2017.
Proteostasis is currently conducting a 14-day
MAD Phase 1 study of PTI-801 (corrector) in healthy volunteers in
the U.S., to be followed by dosing in CF patients. If
positive results are achieved in the Company’s PTI-428 and PTI-801
programs, the Company intends to initiate a triple combination
Proof of Concept (POC) study, which will combine PTI-428, PTI-801
and PTI-808 (also known as PTI-NC-733), in an F508del homozygous
population who are not taking Orkambi®, at the end of 2017.
The study will explore different doses of PTI-808 with fixed dose
combination of PTI-428 and PTI-801.
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 HarborTo 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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