BOSTON, Dec. 11, 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, initial ex-vivo results of
PTI's proprietary cystic fibrosis transmembrane conductance
regulator (CFTR) modulators, PTI-801, PTI-808, and PTI-428, in
individuals with CF who are ineligible for the current standard of
care CFTR modulator therapies due to their genotype. The data are
part of a pan-European strategic initiative, known as HIT-CF (Human
Individualized Therapy of CF), which seeks to accelerate the
development of, and access to, personalized therapies for CF
patients, beginning with those for whom no currently approved CFTR
modulator therapy is indicated.
HIT-CF is sponsored by the European Commission Horizon 2020
program, in which CF-Europe, a patient organization representing
more than 48,000 individuals with CF, collaborates and with the
European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN),
which is recruiting adult CF patients into the ex- vivo
study through its 43 clinical trial centers. HIT-CF collects
tissue samples from CF patients and develops organoids, or
miniaturized organs, that are genetically identical to the patient
donor, and share the same micro-anatomy as the organ from which
they were derived.
As of today, rectal organoids from over 300 subjects have been
collected for functional profiling and of those, 65 have been
tested for response to PTI's investigational drugs. Early results
support the initiation of enrollment of responding subjects into
HIT-CF's clinical trial known as "CHOICES" (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, such as
changes in FEV1 and sweat chloride. CHOICES, which is
expected to initiate in mid-2020, will be the first ever
personalized medicine-based study in CF, with initial data expected
by the end of 2020. Fully funded by the HIT-CF, this trial is
a placebo controlled, double blind, crossover study with an 8-week
treatment period and 6 months of uninterrupted dosing. The
results may serve as the basis for a potential Marketing
Authorization Application with the European Medicines Agency (EMA)
in 2021 through a novel regulatory pathway which is being pursued
jointly by Proteostasis and HIT-CF. The CHOICES clinical
study is part of PTI's broader clinical development strategy for
its CFTR modulator candidates that is already separately funded for
the common genotypes.
Results from the HIT-CF project to date will be presented at the
Keystone Symposia on Tissue Organoids titled "Tissue Organoids as
Models of Host Physiology and Pathophysiology of Disease (J1)"
taking place on January 19-23, 2020
in Vancouver, BC, Canada.
"Proteostasis is honored to have been invited to participate in
the HIT-CF project and is the only company in the group with a
combination of novel CFTR modulators being tested ex-vivo.
We are very enthusiastic about the progress of the study," said
Geoffrey Gilmartin, M.D., M.M.Sc.,
Chief Medical Officer of Proteostasis Therapeutics. "In Europe
alone, there are more than 2,300 adult patients whose genotypes
render them ineligible for approved CFTR modulators and exclude
them from participating in clinical trials with this drug class.
This project's proposed personalized medicine approach is paving a
potential new way to develop and provide access to novel CFTR
modulators for patients with the most dire need for treatment
options that target the cause of the disease. Additionally, based
on an individual patient's disease phenotype and not just the
genetic designation, this approach could also create a new path
towards more effective treatment for all people with CF."
"The inequality in access to CFTR modulators is an acute problem
across Europe where 1 in 5
individuals do not have a F508del mutation. In addition, drug
reimbursement policies are leading to an ever-growing gap between
patients who do, and those who do not have effective treatment
options," said Christiane De Boeck,
Work Package Leader at HIT-CF, and Former President of ECFS. "At
HIT-CF Europe, we believe that novel strategies such as
personalized medicine and development of new treatment options are
central to addressing the inequality of access across the
continent. We are thrilled with these initial results and look
forward to providing additional updates."
About Organoids
Organoids are cell cultures that grow in a culture dish and look
similar to the organ from which they are derived. Because organoids
are made from stem cells, they contain the same mutations as the
person from whom the biopsies are derived. Investigational drugs
which target the basic defect of CF can be used in an organoid
system to evaluate rare mutations where the drugs may have a
positive effect.
Unlike in vitro systems such as human bronchial
epithelial (HBE) cells, which are derived from lungs that have been
removed from CF patients, or the engineered, rat-derived FRT cell
line, the latter has resulted in false positive clinical results,
rectal organoids are cultured from tissues obtained through a
minimally invasive and painless procedure from donors who then
become eligible to participate in a clinical study. Organoids
can provide valuable insights for donors, including their
likelihood of achieving improvements in pulmonary function and
reductions in sweat chloride concentration with CFTR modulators
based on the ex-vivo response to those
drugs.1
About HIT-CF Europe
HIT-CF Europe is a research project which aims to provide better
treatment and better lives for people with cystic fibrosis (CF) and
rare mutations. To achieve this, drug candidates are first tested
on patient-derived organoids in qualified laboratories across
Europe. Subsequently, based on the
measured signal in the organoids, a smaller group of patients will
be invited to participate in a clinical trial with one or more
investigational molecules from a participating pharmaceutical
company.
All participating centers are part of the European Cystic
Fibrosis Society – Clinical Trial Network (ECFS-CTN). The
project has received funding from the European Union's Horizon 2020
research and innovation program under grant agreement number
755021. For more information, visit www.hitcf.org.
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 expected presentation at an upcoming
conference. 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, our expectations regarding our participation in
HIT-CF's pan-European strategic initiative, the potential of
our proprietary combination therapies for the treatment of CF, the
potential benefit of our proprietary combination therapies to
patients, expected timing of patient enrollment in, data from, the
completion of, and reporting top line results of our clinical
studies and cohorts for our clinical programs, including our
planned Phase 2 program and initiation of a pivotal or
registrational study, 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),
in the commercialization and acceptance of new therapies, 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
1 Berkers et al, Rectal Organoids Enable
Personalized Treatment of Cystic Fibrosis Cell Reports 26,
1701–1708, February 12, 2019
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SOURCE Proteostasis Therapeutics, Inc.