BOSTON, Dec. 17, 2019 /PRNewswire/ -- Proteostasis
Therapeutics, Inc. (NASDAQ: PTI), a clinical stage
biopharmaceutical company dedicated to the discovery and
development of groundbreaking therapies to treat cystic fibrosis
(CF), today announced positive topline results from the Company's
global, multicenter, randomized, placebo-controlled, 28-day, Phase
2 study evaluating its proprietary cystic fibrosis transmembrane
conductance regulator (CFTR) modulator combinations in F508del
homozygous and heterozygous CF subjects 18 years of age and
older.
The trial is designed to assess the efficacy, safety and
tolerability of PTI's once-daily proprietary combinations, 300 mg
of dirocaftor (PTI-808) and 600 mg of posenacaftor (PTI-801), with
or without 10 mg of nesolicaftor (PTI-428), or placebo, over a four
week treatment period. A total of 28 F508del homozygous and
40 F508del heterozygous subjects were enrolled into the doublet,
triplet or placebo arms. The compounds were generally well
tolerated and the majority of reported adverse events were mild to
moderate in severity. Most subjects enrolled in the Phase 2 study
carried a high disease burden, with over 80 percent of subjects
trying and failing to enroll into trials of currently approved
modulators due to ineligibility.
Homozygous subjects receiving the triple combination experienced
a mean absolute improvement in ppFEV1 of 8 percentage
points over pooled placebo at day 28 (p ≤ 0.01, 95% CI 3, 12;
n=11). Improvements in lung function were the highest in high
disease burden subgroups, predefined as subjects with
ppFEV1 <70 at baseline (+10 ppFEV1, n=9),
subjects with at least 2 pulmonary exacerbations within 12 months
prior to study (+12 ppFEV1, n=5) and poor responders to
prior CFTR modulators (+12 ppFEV1, n=7). Sweat chloride
concentration in homozygous subjects receiving dirocaftor,
posenacaftor and nesolicaftor demonstrated a mean improvement of
-29 mmol/L at day 28 (p < 0.0005, 95% CI -42, -16; n=11)
compared to pooled placebo.
In the homozygous population, the magnitude of the improvements
in the ppFEV1 and sweat chloride concentration at day 28
with the dirocaftor, posenacaftor and nesolicaftor were higher than
those observed in subjects receiving the double combination of
dirocaftor and posenacaftor. These observations highlight the
contribution of nesolicaftor to the overall efficacy of the triple
combination.
In PTI's first clinical study with F508del heterozygous
population, 40 subjects with at least 26 different genotypes were
enrolled. As expected, given the mechanism of action of CFTR
modulators, a broad range of ppFEV1 and sweat chloride
responses were observed in these subjects. For those on active
treatment, ppFEV1 responses ranged from -13 to +20 and
sweat chloride concentration responses ranged from +12 mmol/L to
-79 mmol/L. Changes in sweat chloride concentration
were statistically significant (p<0.01). Responder rate,
defined as ppFEV1 improvement of 5 percentage points or
more, was three times as high in subjects who received active vs.
placebo. Mean changes in ppFEV1 were not
statistically significant in the heterozygous population.
"Evidenced by the variability of subject response and
tolerability to currently approved CFTR modulators, it remains
clear that the CF community is in need of additional CFTR modulator
options. The latest data from the dirocaftor, posenacaftor and
nesolicaftor combination suggests that, even in a population with
high disease burden and including subjects who were not eligible
for studies of currently approved CFTR modulators, this triple
combination demonstrated remarkable outcomes across key study
endpoints and performed well in the most challenging disease
settings, including those subjects with at least two pulmonary
exacerbations within 12 months prior to study entry," said
Jennifer Taylor-Cousar, M.D.,
M.S.C.S., Professor of Medicine and Pediatrics, and Co-Director and
CF Therapeutics Development Network Center Director of the Adult CF
Program at National Jewish Health. "I look forward to the
upcoming MORE and CHOICES pivotal studies, and to seeing people
with CF potentially benefit from a broader treatment
armamentarium."
Based on these results, the Company is planning to launch a
global, Phase 3, randomized, placebo-controlled, MORE trial
(Modulator Options to RestorE CFTR study) in CF subjects with the
common F508del homozygous mutation, beginning in 2020. The MORE
trial complements the CHOICES trial (Crossover trial based
on Human Organoid Individual response in CF
- Efficacy Study), which is designed to evaluate the
translation of organoid ex-vivo response to
potential clinical benefit in patients with rare mutations.
CHOICES, which is also expected to initiate in 2020, will be the
first ever personalized medicine-based study in CF.
"We look forward to advancing our triple combination into a
pivotal study next year, while simultaneously pursuing a
personalized medicine clinical and regulatory pathway together with
the HIT-CF funded through the European Commission Horizon 2020
program. We are very grateful to the patients, their families and
healthcare providers who have supported PTI in our pursuit of
delivering more choices to people with CF and to providing the
benefit of CFTR modulators to all, regardless of mutation status,"
said Geoffrey Gilmartin, M.D.,
M.M.Sc., Chief Medical Officer of Proteostasis.
Conference Call and Webcast
Proteostasis will hold a conference call and accompanying
webcast today, December 17, at 8:30
a.m. ET to discuss the data announced today. The
conference call can be accessed by dialing (844) 534-7315
from the United States or (574) 990-3007 from
outside the United States and referring to conference ID
4291402. A live webcast and accompanying slide presentation will be
available on the Investor Events 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 Dirocaftor (PTI-808), Posenacaftor (PTI-801) and
Nesolicaftor (PTI-428)
Nesolicaftor (PTI-428) is an investigational CFTR amplifier in
development for the treatment of CF in patients with at least
one F508del mutation in the CFTR gene, as part of PTI's
proprietary triple combination regimen that includes dirocaftor
(PTI-808), a novel potentiator, and posencaftor (PTI-801), a
third-generation CFTR corrector. Posencaftor received Fast Track
Designation from the U.S. Food and Drug Administration (FDA).
In May 2019, nesolicaftor received Orphan Drug
Designation (ODD) from the European Commission (EC).
In addition to ODD from the EC, nesolicaftor has ODD,
Breakthrough Therapy Designation and Fast Track Designation from
the FDA.
About Proteostasis Therapeutics, Inc.
Proteostasis Therapeutics, Inc. is a clinical stage
biopharmaceutical company developing small molecule therapeutics to
treat cystic fibrosis and other diseases caused by dysfunctional
protein processing. Headquartered in Boston, MA,
the Proteostasis Therapeutics team focuses on identifying
therapies that restore protein function. 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 potential of our proprietary combination
therapies for the treatment of CF, the potential benefit to
patients of our proprietary combination therapies, expected timing
of patient enrollment in, data from, the completion of, our
clinical studies and cohorts for our clinical programs, including
our planned Phase 3 program and initiation of a registrational or
pivotal study. 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 that FDA or other regulatory agency comments delay,
change or do not permit trial commencement, or intended label, or
the FDA or other regulatory agency 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 a competitive clinical environment, 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 the endorsement, if any, by therapeutic
development arms of CF patient advocacy groups (and the maintenance
thereof), and those set forth in our Annual Report on Form 10-K for
the year ended December 31, 2018, our
Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 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
/ Claudia Styslinger
Argot Partners
212.600.1902
david@argotpartners.com / claudia@argotpartners.com
Media:
David Rosen
Argot Partners
212.600.1902
david.rosen@argotpartners.com
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SOURCE Proteostasis Therapeutics, Inc.