On December 11, 2017, spokespersons of the Company presented the information in the
presentation slides attached hereto as Exhibit 99.2, and announced the following information:
Results of
PTI-428
Meet Efficacy Endpoint in
28-day
Study in CF Patients on Background Orkambi
Proteostasis 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 ppFEV
1
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.
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 ppFEV
1
below 70% (+3.3 percentage points) while the changes in the group
with FEV
1
³
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 ppFEV
1
compared to placebo for patients who had lower baseline
ppFEV
1
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.
Preliminary Ad Hoc Analysis of
PTI-801
in Ongoing
14-day
Study in CF
Patients on Background Orkambi
The 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. The Company expects to report additional data from this study in the first quarter of 2018.
1
|
Orkambi
®
is a registered trademark from Vertex Pharmaceuticals, Inc.
|
PTI-808
Completes Safety and PK Profile from SAD and MAD Study in
Healthy Volunteers
A 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.
Safe Harbor
To the extent that statements in this Form
8-K
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, potentially 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 Form
8-K
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, and statements regarding the potential suitability of
PTI-808
and of our triple combination therapy for daily dosing. Forward-looking statements made in this Form
8-K
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 that 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.
The above information is not an admission as to the materiality of any information therein. The Company undertakes no duty or obligation to update or revise
the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases or
through other public disclosures.