PolyPid Announces Positive Topline Results from Phase 3 SHIELD II Trial: D-PLEX 100 Demonstrated Significant Reduction in Surgical Site Infections and Successfully Met Primary and All Key Secondary Endpoints D-PLEX 100 s

PolyPid Announces Positive Topline Results from

Phase 3 SHIELD II Trial: D-PLEX100 Demonstrated Significant Reduction in Surgical

Site Infections and Successfully Met Primary and All Key Secondary Endpoints

PETACH TIKVA, Israel, June 9, 2025 -- PolyPid

("PolyPid" or the "Company"), a late-stage biopharma company

aiming to improve surgical outcomes, today announced positive topline results from its pivotal SHIELD

II Phase 3 trial of D-PLEX100 for the prevention of SSIs in patients undergoing abdominal colorectal surgery with large

incisions, which has received Fast Track designation from the FDA.

"The positive results of our Phase 3 pivotal trial provide clear

and compelling evidence of D-PLEX100's ability to significantly reduce SSIs, a major burden on patients and healthcare

systems, while improving clinical outcomes for both patients and physicians," said Dikla Czaczkes Akselbrad, Chief Executive Officer

of PolyPid. "D-PLEX100 has the potential to meaningfully lower costs for hospitals and payers, and we believe it will

be a valuable addition to the standard of care. Targeting a total addressable U.S. market of over 12 million annual surgeries and a significant

unmet need, D-PLEX100 has the potential to make a substantial market impact. We remain on track for an NDA submission in early

2026 and believe these robust data will serve as a strong catalyst for advancing our global partnership discussions. We are deeply grateful

to the patients, principal investigators, and study teams who made this milestone possible."

Key findings from SHIELD II study include:

Image: SHIELD II Results on Primary Endpoint

and First Key Secondary Endpoint

"The risk of surgical site infection in the colorectal patient

population has recently been documented to approach 23%2 in patients with multiple comorbid risk factors," said Charles

E. Edmiston, Jr., MS, PhD, CIC, FIDSA, FSIS, FAPIC Emeritus Professor of Surgery. "These topline results provide clinical practitioners

with a novel, innovative strategy for reducing postoperative infection risk in patients undergoing colorectal surgery with large wound

incisions. Based on the trial findings, particularly the significant risk-reduction benefit by reducing in-wound sepsis risk, I anticipate

D-PLEX100 technology will be rapidly embraced as a critical component to the current evidence-based surgical care bundle for

colorectal surgery following FDA approval."

Additional results from the SHIELD II trial will be presented at an

upcoming medical conference.

Conference Call Dial-In & Webcast Information:

A replay of the presentation will be available on the Company's

Investor Relations Events and Presentations webpage following the event.

SHIELD II (Surgical site Hospital acquired Infection prEvention

with Local D-PLEX) is a prospective, multinational, randomized, double blind Phase 3 trial designed to assess the efficacy and safety

of D-PLEX100 administered concomitantly with standard of care ("SoC"), which includes prophylactic systemic

antibiotics, compared to SoC alone arm, in the prevention of post abdominal-surgery incisional infection in patients undergoing abdominal

colorectal surgeries with large incisions. The primary endpoint of the trial is measured by the proportion of subjects with either a surgical

site infection ("SSI") event as determined by a blinded and independent adjudication committee, reintervention, or mortality

for any reason within 30 days post-surgery. Patient safety will be monitored for an additional 30 days. The trial will enroll patients

in centers in the United States, Europe and Israel.

D-PLEX100, PolyPid's

lead product candidate, is designed to provide local prolonged and controlled anti-bacterial activity directly at the surgical site to

prevent SSIs. Following the administration of D-PLEX100 into the surgical site, the PLEX (Polymer-Lipid Encapsulation matriX)

technology pairs with Active Pharmaceutical Ingredients, enabling a prolonged and continuous release of the broad-spectrum antibiotic

doxycycline, resulting in a high local concentration of the drug for a period of 30 days for the prevention of SSIs, with additional potential

to prevent SSIs caused by antibiotic-resistant bacteria at the surgical site. D-PLEX100 received Breakthrough Therapy

designation from the U.S. Food and Drug Administration for the prevention of SSIs in patients undergoing elective colorectal

surgery. D-PLEX100 is currently in Phase 3 SHIELD II trial for the prevention of surgical site infections in patients

undergoing abdominal colorectal surgery with large incisions.

PolyPid Ltd. (Nasdaq: PYPD)

is a late-stage biopharma company aiming to improve surgical outcomes. Through locally administered, controlled, prolonged-release therapeutics,

PolyPid's proprietary PLEX (Polymer-Lipid Encapsulation matriX) technology pairs with Active Pharmaceutical Ingredients (APIs),

enabling precise delivery of drugs at optimal release rates over durations ranging from several days to months. PolyPid's lead product

candidate D-PLEX100 is in a Phase 3 clinical trial for the prevention of abdominal colorectal surgical site infections.

In addition, the Company is currently in preclinical stages to test the efficacy of OncoPLEX for the treatment of solid tumors, beginning

For additional Company information, please

visit http://www.polypid.com and

Forward-looking Statements

This press release contains "forward-looking statements"

within the meaning of the Private Securities Litigation Reform Act and other securities laws. Words such as "expects," "anticipates,"

"intends," "plans," "believes," "seeks," "estimates" and similar expressions

or variations of such words are intended to identify forward-looking statements. For example, the Company is using forward-looking statements

when it discusses the safety, efficacy and benefits of D-PLEX100, D-PLEX100's potential to meaningfully lower

costs for hospitals and payers, the expected submissions of an NDA to the FDA and MAA and the timing thereof; the Company's belief

that the data results will serve as a strong catalyst for advancing its global partnership discussions; D-PLEX100 potential

to make a substantial market impact; and the anticipation that D-PLEX100 technology will be rapidly embraced as a critical

component to the current evidence-based surgical care bundle for colorectal surgery following FDA approval. Forward-looking statements

are not historical facts, and are based upon management's current expectations, beliefs and projections, many of which, by their

nature, are inherently uncertain. Such expectations, beliefs and projections are expressed in good faith. However, there can be no assurance

that management's expectations, beliefs and projections will be achieved, and actual results may differ materially from what is

expressed in or indicated by the forward-looking statements. Forward-looking statements are subject to risks and uncertainties that could

cause actual performance or results to differ materially from those expressed in the forward-looking statements. For a more detailed description

of the risks and uncertainties affecting the Company, reference is made to the Company's reports filed from time to time with the Securities

and Exchange Commission, including, but not limited to, the risks detailed in the Company's Annual Report on Form 20-F filed on February

26, 2025. Forward-looking statements speak only as of the date the statements are made. The Company assumes no obligation to update forward-looking

statements to reflect actual results, subsequent events or circumstances, changes in assumptions or changes in other factors affecting

forward-looking information except to the extent required by applicable securities laws. If the Company does update one or more forward-looking

statements, no inference should be drawn that the Company will make additional updates with respect thereto or with respect to other forward-looking

References and links to websites have been

provided as a convenience, and the information contained on such websites is not incorporated by reference into this press release. PolyPid is

not responsible for the contents of third-party websites.