Proteostasis Therapeutics and CF Europe Announce Completion of Patient Enrollment for CHOICES, the First-Ever Personalized Medicine-Based Study in Cystic Fibrosis


BOSTON, Feb. 24, 2020 /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) and CF Europe, the federation of 48 national CF Associations in Europe, today announced the completion of enrollment of 502 patients with CF for HIT-CF, a European-based initiative that is paving the path to personalized medicine through the CHOICES clinical trial.  CHOICES will test PTI drug combinations in an ex vivo study and then in a clinical trial to assess the predictability of the organoid assay for clinical benefit.  

For the ex vivo portion, organoids derived from tissue samples provided by patients enrolled in the study are evaluated for responsiveness to investigational CFTR modulators, including Proteostasis' CFTR potentiator, corrector and amplifier, dirocaftor (DIR), posenacaftor (POS) and nesolicaftor (NES), respectively.  Based on an individual's organoid response, patients will be invited to progress to the next portion of the study which is a placebo controlled, double blind, crossover study known as the CHOICES trial (Crossover trial based on Human Organoid Individual response in CF - Efficacy Study).

The results from CHOICES may serve as the basis for a potential Marketing Authorization Application with the European Medicines Agency (EMA) in 2021 through a novel regulatory pathway. This strategic initiative is led by the HIT-CF consortium, funded through the European Commission's Horizon 2020 program. The CHOICES clinical study is part of PTI's broader clinical development strategy for its CFTR modulator candidates that also includes the MORE trial in CF subjects with the most common F508del homozygous genotype.

"The enrollment of more than 500 patients across Europe in the first phase of the HIT-CF project is a testament to the strategic imperative this program holds for both the patient and treatment community," said Geoffrey Gilmartin, M.D., M.M.Sc., Chief Medical Officer of Proteostasis Therapeutics. "With the successful translation of activity from organoids to patients, this study has the potential to usher in a personalized medicine approach to CF.  This approach would begin with patients who have less common mutations, but could ultimately serve the broader CF community by delivering personalized treatment choices that maximize benefit based on each patient's responsiveness to therapy."

"We are excited that Proteostasis is participating in the HIT-CF project and supporting our efforts to bring CF treatment to more people across Europe," said Jacquelien Noordhoek, President of CF Europe and representative of the Netherlands Cystic Fibrosis Society (NCFS). "Enrolled individuals are a portion of the approximately 2,300 adults in the European patient registry who are not eligible for any currently approved modulator due to their genotype and the HIT-CF project represents the only option to explore potential benefit of disease modifying drugs for this group.  Putting patients with CF first is our highest priority. We are looking forward to continuing our partnerships and providing Europeans with CF the best possible care."

About Organoids

Organoids are cell cultures that grow in a culture dish with properties similar to those of 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 (which has had 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 drugsi.

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 clinical trials with investigational molecules from participating pharmaceutical companies.

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

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

Safe Harbor

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to statements regarding the potential of PTI drug combinations, expectations regarding ex vivo testing of our proprietary combinations in organoids and clinical evaluation in CF patients, the expected timing for enrollment, completion and reporting of results of our CHOICES Phase 3 clinical trial, our commitment to expanding available therapeutic options for CF patients and the intended goals of the CHOICES trial and the ability to serve as a potential basis for future marketing approval. 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, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of 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 potential of our proprietary combination therapies for the treatment of CF, the potential benefit of our proprietary combination therapies to patients, expected completion of our clinical studies and cohorts for our clinical programs, 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). For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. We assume no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, unless required by law.


David Pitts / Claudia Styslinger
Argot Partners
212.600.1902 /

David Rosen
Argot Partners

HIT-CF Project Coordination:
HIT-CF Consortium
University Medical Centre Utrecht (The Netherlands)

i 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.

Company Codes: NASDAQ-NMS:PTI

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