Proteostasis Therapeutics, Inc. (NASDAQ:PTI), a clinical stage
biopharmaceutical company dedicated to the discovery and
development of groundbreaking therapies to treat cystic fibrosis
(CF) and other diseases caused by dysfunctional protein processing,
today announced positive study results across all three of the
company’s CF pipeline programs. These include a study in CF
subjects for PTI-428, a cystic fibrosis transmembrane conductance
regulator (CFTR) amplifier; interim data for a study in CF subjects
for PTI-801, a new generation CFTR corrector; and studies in
healthy volunteers for PTI-808, a CFTR potentiator, and the
combination of PTI-428, PTI-801 and PTI-808. The results
support the goal of studying the Company’s novel CFTR modulators in
doublet and triplet combinations in CF subjects.
Results of PTI-428 Meet Efficacy
Endpoint in 28-day Study in CF Patients on Background
OrkambiProteostasis announced that it has completed its
Phase 2 study designed to evaluate the efficacy, safety, and
tolerability of 50 mg once-a-day of PTI-428 over a 28-day treatment
of CF patients on background Orkambi®1 (lumacaftor/ivacaftor).
The addition of PTI-428 to Orkambi® demonstrated mean
absolute improvements in ppFEV1 of 5.2 percentage points from
baseline compared to placebo (p<0.05), with mean relative
improvements of 9.2 percent (p<0.05). This treatment effect was
achieved by day 14 and sustained through 28 days of dosing.
“This is an important first step towards
translating the scientific potential of the first and only genotype
agnostic CFTR modulator in development, and its ability to enhance
Orkambi by selectively increasing the production of the CFTR
protein,” said Dr. Patrick Flume, a clinical investigator at the
Medical University of South Carolina, a CFFT Therapeutics
Development Network center, who is participating in the PTI-428 and
PTI-801 clinical studies. “I look forward to seeing PTI-428
evaluated in further combination studies, with the goal of fully
elucidating the potential of this unique CFTR amplifier.”
The two registrational phase 3 studies of
Orkambi®, TRAFFIC and TRANSPORT, showed that magnitude of response
to Orkambi® varied according to patient lung function at screening,
suggesting that the overall efficacy was mainly driven by the
subgroup with baseline ppFEV1 below 70% (+3.3 percentage points)
while the changes in the group with FEV1 ≥70% were not
statistically significant. A similar analysis was performed in the
28-day study with PTI-428 and it showed an average +6.6 percentage
points increase (p<0.05) in absolute ppFEV1 compared to placebo
for patients who had lower baseline ppFEV1 value (<70%). The
results of the subgroup analysis are consistent with Phase 3 data
with Orkambi®, suggesting that PTI-428 potentially amplifies the
Orkambi® effect in the responder population.
Additional exploratory endpoints in the study
included measurement of changes in sweat chloride and CFTR
expression in nasal epithelia. In this study, a positive increase
in CFTR protein from baseline was observed in PTI-428 treated
subjects and the magnitude of change was consistent with the
changes in CFTR protein levels observed in an in vitro human
bronchial cell (HBE) model. In contrast, changes in sweat
chloride did not correlate with changes in lung function.
The 28-day study continues to confirm the safety
profile of PTI-428 in that it was generally well tolerated and
lacked clinically meaningful drug-drug interactions with ivacaftor
and lumacaftor. Fourteen of 20 subjects receiving
PTI-428 and two of four subjects receiving placebo experienced at
least one treatment emergent adverse event. There were no serious
adverse events and there were 2 adverse events that led to study
discontinuation. Both cases were thrombocytopenia of mild grade and
comparable magnitude and value. One occurred while a subject was on
Orkambi® only and one in a subject receiving PTI-428, with both
subjects resolving spontaneously.
“The ability to capture an improvement in
absolute ppFEV1 along with a targeted increase in the CFTR protein
at 50 mg of PTI-428 indicates that we have been able to identify a
starting dose that will guide us for future dose optimization in
combination studies with our proprietary potentiator and
corrector,” said Meenu Chhabra, president and CEO.
Preliminary Ad Hoc Analysis of PTI-801
in Ongoing 14-day Study in CF Patients on Background
OrkambiThe Company has also shared initial data from the
first five subjects (four PTI-801 treated and one placebo) of the
first dose level tested in the 14-day dosing study of PTI-801 in CF
patients on background Orkambi® therapy. All four subjects
who received once-a-day 100 mg of PTI-801 have completed two weeks
of dosing. The pharmacokinetic (PK) profile observed from these
four subjects is consistent with the PK profile observed for
healthy volunteers. These initial data also showed no clinically
meaningful drug-drug interactions with either lumacaftor or
ivacaftor. There were no serious adverse safety events
reported that were considered as possibly drug related. Mean
absolute improvements in ppFEV1 of approximately 4 percentage
points from baseline, with mean relative improvements of
approximately 7 percent, were observed in the four PTI-801 subjects
who have completed two weeks of dosing to date. The first cohort of
up to 20 patients is still recruiting with enrollment expected to
complete in Q1 2018.
“This initial data begins to validate the in
vitro profile of PTI-801 and its potential to bolster efficacy for
subjects on Orkambi®. We are eager to explore a dose response in
the next planned cohort with 200 mg of once a day dosing,” said Ms.
Chhabra.
PTI-808 Completes Safety and PK Profile
from SAD and MAD Study in Healthy VolunteersA total of 48
healthy volunteers have participated and completed the study of up
to 300 mg of once-a-day, orally dosed PTI-808, a novel CFTR
potentiator that was tested in single and multiple dose cohorts.
PTI-808 was found to be generally well tolerated. One subject
experienced a serious adverse event from a pre-existing condition
of transverse myelitis. This serious adverse event was considered
unlikely to be related to the study drug. No adverse events leading
to discontinuation of treatment were reported. All other
adverse events that have been reported to date were of mild or
moderate severity. Preliminary PK assessment of PTI-808 suggest
that it could potentially be suitable for once daily
dosing.
Co-administration of PTI-428, PTI-808
and PTI-801 in Healthy Volunteers Completed PTI completed
a healthy volunteer co-administration study of its three
proprietary CFTR modulators testing safety and tolerability in 20
subjects. Safety and PK profiles achieved with seven days of
once-a-day oral dosing of PTI-428, PTI-801 and PTI-808 indicate
these compounds were generally well-tolerated and could potentially
be amenable for once a day dosing. No SAEs or AEs leading to
discontinuation of treatment were reported. The PK data
demonstrated a lack of clinically meaningful drug-drug
interactions. Combination study protocols have been reviewed
by key patient advocacy and regulatory authorities in US and
Europe.
“The phase 2 data with PTI-428, along with
initial clinical evidence with PTI-801 and the completion of
co-administration safety and PK studies with all three CFTR
modulators in healthy volunteers further cements our progress
towards combination development with our proprietary compounds in
the CF patient population,” said Ms. Chhabra. “We look
forward to initiating a doublet study of PTI-801 and PTI-808 in CF
subjects and progressing towards a triple combination study in CF
subjects in 2018.”
Conference Call and Webcast
Proteostasis will hold a conference call and
accompanying webcast today, December 11, 2017, at 5:00 p.m. ET to
discuss the data announced today. The conference call can be
accessed by dialing 1-844-534-7315 from the United States or
1-574-990-3007 from outside the United States and referring to
conference ID 8786987. A live webcast and accompanying slide
presentation will be available on the Event Calendar page in the
Investors & Media section of the company’s website,
www.proteostasis.com. A replay of the webcast will be available on
the company’s website shortly after the conclusion of the
conference call.
About Proteostasis Therapeutics,
Inc.
Proteostasis Therapeutics, Inc. is a clinical
stage biopharmaceutical company developing small molecule
therapeutics to treat cystic fibrosis (CF) and other diseases
caused by dysfunctional protein processing. 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 the completion
of, our clinical studies and cohorts for PTI-428, PTI-801, PTI-808
and our dual and triple combination therapy candidates.
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 by the Company (noting that these results are
based 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 Quarterly Report on
Form 10-Q for the quarter ended September 30, 2017 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.
1 Orkambi® is a registered trademark from Vertex
Pharmaceuticals, Inc.
CONTACTS:
Investors:David PittsArgot
Partners212.600.1902david@argotpartners.com
Media:Eliza SchleifsteinArgot
Partners973.361.1546eliza@argotpartners.com
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