Proteostasis Therapeutics Announces New Publication on the Mechanism of Action of a Novel Class of CFTR Modulators Called Amplifiers in the Journal of Cystic Fibrosis


BOSTON, Feb. 25, 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), today announced the publication of nonclinical data on the mechanism of action of nesolicaftor (PTI-428).  The article, entitled "Amplifiers co-translationally enhance CFTR biosynthesis via PCBP1-mediated regulation of CFTR mRNA," was published online in the Journal of Cystic Fibrosis on February 14, 2020. 

The Dukovski et al., paper demonstrates that amplifiers bind directly to poly(rC)-binding protein 1 (PCBP1). PCBP1 belongs to a large family of RNA-binding proteins that regulate the production of cystic fibrosis transmembrane conductance regulator (CFTR) just before the protein prepares to fold and assemble itself for delivery to its final destination in the cell membrane where it works by regulating ion flow. The authors show that the binding of amplifiers for PCBP1 is specific to CFTR because the binding affinity is enhanced through a portion of mRNA that is only present in CFTR. This leads to improved stability of CFTR mRNA and results in greater CFTR protein production.

"Even in healthy individuals, the CFTR protein is an undeniably complex and inefficient protein to produce, given that 80% of it is degraded and eliminated. Improving the production of CFTR by delivering a new class of CFTR modulators was made possible because of our pioneering work in elucidating the function of the proteostasis network.  The proteostasis network consists of a multitude of pathways and cellular processes that serve to achieve protein quality control, that is to make the decision to drive CFTR towards folding and trafficking versus destruction," said Jeffery W. Kelly, Ph.D., co-founder of Proteostasis Therapeutics, Inc. and a co-author on the publication. "These results provide new insight into the cellular regulation of CFTR biosynthesis and further advance the understanding of CF biology for the benefit of the scientific community that is searching for new therapeutic approaches to this serious and life limiting disease."

By improving the efficiency by which the CFTR protein is produced, amplifiers are orthogonally delivering more protein for folding and trafficking and thereby increasing CFTR function when coupled with a corrector and a potentiator. Thus, amplifiers represent a promising new and mechanistically novel class of CFTR therapeutic that may be useful as a monotherapy or in combination with other CFTR modulators.

The full publication can be accessed here.

About 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.  It is part of PTI's proprietary triple combination regimen that includes dirocaftor (PTI-808), a novel potentiator, and posenacaftor (PTI-801), a third-generation CFTR corrector. Nesolicaftor has been shown to work early during CFTR biogenesis to increase levels of newly synthesized CFTR protein, suggesting potential therapeutic benefits in combination with CFTR correctors and potentiators.  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. Nesolicaftor, the most advanced amplifier in development at PTI, has been tested in 250 healthy volunteers and patients with CF combined.

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 nesolicaftor and our proprietary combination therapies for the treatment of CF and the potential benefit to patients of our proprietary combination therapies.  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, expected timing of patient enrollment in our clinical studies and cohorts for our clinical programs, including our planned Phase 3 programs and initiation of registrational or pivotal studies, submission of marketing authorization applications, 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


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Company Codes: NASDAQ-NMS:PTI

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