***PTI-801 Receives FDA Fast Track Designation; Phase 1 Study Underway
***IND Submission for PTI-808 Planned for 2Q17
***Phase 1 Study of PTI-428 Updated and Ongoing; Results Expected 2Q17
“Today, CFTR modulator triple combinations represent the greatest promise for delivering maximum efficacy for the vast majority of CF patients and have become the central focus in a rapidly evolving clinical landscape,” said Meenu Chhabra, president and chief executive officer of Proteostasis Therapeutics. “Preclinical data suggest that Proteostasis’ proprietary triple combination solution of an amplifier (PTI-428), a corrector (PTI-801) and a potentiator (PTI-808) has the potential to demonstrate best-in-class efficacy because it is the only triple combination that addresses separate aspects of CFTR dysfunction in an entirely orthogonal manner from protein synthesis to processing to function. To realize this potential in an increasingly crowded clinical environment, we are pivoting our PTI-428 program to ex-U.S. clinical sites, initiating the clinical development of PTI-801 in regions where Orkambi is approved and expect to file an IND for PTI-808 in the second quarter. Our goal is to establish efficacy for PTI-428 and PTI-801 in an Orkambi population, and thus start the proof of concept study for our triple combination by the end of the year.”
Corporate Updates
PTI-428 – Fast Track-Designated CFTR Amplifier
To date, Proteostasis has reported preliminary safety, pharmacokinetic and exploratory biomarker data from both single and multiple ascending dose cohorts in its healthy volunteer trial of PTI-428. The drug was well tolerated and no drug-related SAEs were identified. Subjects who achieved a threshold concentration approximating EC70 had a two-fold increase in cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein which returned to baseline in the follow-up period.
Based on this nasal biomarker data, preclinical studies, and study precedent for other CFTR modulator programs, the Company now aims to report preliminary data in the second quarter from at least 8 CF subjects from a cohort of stable Orkambi patients dosed with PTI-428 for 7 days followed by a 7-day follow-up period. After wash-out, these subjects will then be eligible to enroll in a 28-day dosing cohort. Initial data will include safety and pharmacokinetics (PK) as well as changes in CFTR mRNA, protein, sweat chloride and lung function as measured by forced expiratory volume in 1 second, or FEV1. Data from the 28-day dosing cohort is expected in the second half of 2017.
The delay in study timeline from first quarter to second quarter stems from a highly competitive clinical development environment in the U.S., including several recent CF study starts for investigational agents that, unlike PTI-428, have received Therapeutics Development Network (TDN) endorsement and ranking. The Company believes the TDN, the development arm of the Cystic Fibrosis Foundation Therapeutics, Inc., can play a key role in helping access U.S. study participants. The Company has an active IND with the U.S. Food and Drug Administration (FDA) for PTI-428 and, following deferred endorsement, continues discussions with the TDN on its review of PTI-428.
To ensure the continued, rapid development of PTI-428, the Company expects to focus substantial resources toward European clinical development. To this end, the Company has sought and received endorsement and prioritization in Europe by the Clinical Trial Network (CTN), which is the development network of the European Cystic Fibrosis Society. In addition, PTI-428 has been reviewed and approved for clinical study by the Medicines and Healthcare products Regulatory Agency (UK) and Health Canada.
PTI-801, PTI-808 and PTI-NC-733 – Second Generation Fast Track-Designated CFTR Corrector, Potentiator and Triple Combination Therapy
(from GlobeNewswire)
