By M. Marin

NASDAQ:PYPD

Innovative Drug Delivery Platform (PLEX Technology)

PolyPid Ltd. (NASDAQ:PYPD) is a late clinical stage biopharma company focused on developing locally administered, prolonged-release therapeutics using its proprietary Polymer-Lipid Encapsulation matriX (PLEX) technology, which enables the controlled delivery of medications directly at the surgical site over extended periods ranging from days to several months. The PLEX delivery system is designed to improve surgical outcomes and enhance the efficacy of treatments while minimizing side effects. PolyPid's lead asset is D-PLEX₁₀₀, which it is studying for the treatment of patients undergoing abdominal surgery.

The PLEX platform is flexible and can deliver a variety of therapies, including small molecules, proteins, peptides, and nucleic acids. In addition to studying the efficacy of D-PLEX₁₀₀ in treating abdominal surgery patients, the company also expects to study it for the treatment of patients who require orthopedic surgery. PolyPid also has OncoPLEX in its product pipeline for treatment in oncology patients undergoing surgery.

Advancing Lead Candidate D-PLEX₁₀₀ Through Clinical Trials

PolyPid's lead asset, D-PLEX₁₀₀, is a novel formulation intended to prevent surgical site infections (SSIs) in patients undergoing abdominal colorectal surgery. The company is currently conducting a pivotal Phase 3 clinical trial of D-PLEX₁₀₀, SHIELD (Surgical site Hospital acquired Infection prEvention with Local D-PLEX) II.

SHIELD II is a randomized, double blind Phase 3 trial designed to assess the efficacy and safety of D-PLEX₁₀₀ alongside standard of care therapies compared to standard of care alone in preventing post abdominal-surgery incisional infection in patients with large incisions.

In March 2025, PolyPid announced the successful completion of patient enrollment in the SHIELD II trial. The trial enrolled 800 patients in medical centers in the U.S., Europe and Israel. The independent Data Safety Monitoring Board (DSMB) had recommended that PolyPid conclude enrollment at the lowest sample size reassessment option, as it believes it will be sufficient to provide statistical significance of the potential positive efficacy of D-PLEX₁₀₀. The company viewed the DSMB’s enrollment recommendation as a positive that suggests the positive efficacy signals from D-PLEX₁₀₀ and believes the study has been derisked significantly. Importantly, to date, no safety issues related to D-PLEX₁₀₀ have been observed in the SHIELD II trial.

The company expects to report top-line results by the end of 2Q25. Depending on the top-line results, PolyPid intends to submit an NDA (New Drug Application) to the FDA in early 2026 to leverage D-PLEX₁₀₀ Fast Track and Breakthrough Therapy designations and thereby expedite the path to potential regulatory approval.