PolyPid starts FDA NDA review for D-PLEX100

PolyPid Ltd. has begun submitting a New Drug Application to the U.S. FDA for its lead product, D-PLEX₁₀₀, to prevent surgical site infections in patients undergoing colorectal surgery.

Rhea-AI Filing Summary

PolyPid Ltd. has begun submitting a New Drug Application to the U.S. FDA for its lead product, D-PLEX₁₀₀, to prevent surgical site infections in patients undergoing colorectal surgery. The NDA is being filed under Fast Track designation, allowing a rolling review, and the first Chemistry, Manufacturing and Controls and nonclinical modules have been submitted, with the clinical section expected in the second quarter of 2026.

D-PLEX₁₀₀ uses PolyPid’s Kynatrix delivery technology to release the antibiotic doxycycline directly at the surgical site over 30 days. In the Phase 3 SHIELD II trial, it achieved a statistically significant 60% relative risk reduction in infection rates after abdominal colorectal surgery and has received Breakthrough Therapy Designation from the FDA. PolyPid is also advancing negotiations for a U.S. commercialization partnership.

Positive

• D-PLEX₁₀₀ advances into FDA NDA review under Fast Track designation, moving PolyPid’s lead asset from late-stage development into the regulatory approval phase for prevention of surgical site infections in colorectal surgery.
• Strong Phase 3 efficacy signal supporting the NDA: the SHIELD II trial showed a statistically significant 60% relative risk reduction in surgical site infections after abdominal colorectal surgery (p=0.0013).
• Regulatory accelerators in place, including FDA Breakthrough Therapy Designation and Fast Track with rolling review, which together may streamline and prioritize assessment of D-PLEX₁₀₀.
• Commercial path preparation is underway, with the company stating that negotiations for a U.S. commercialization partnership for D-PLEX₁₀₀ are on track.

Negative

• None.

Insights

Biopharma regulatory analyst

PolyPid advances D-PLEX₁₀₀ into FDA review with strong Phase 3 data and expedited designations.

PolyPid has initiated an FDA New Drug Application for D-PLEX₁₀₀ to prevent surgical site infections in colorectal surgery, using the agency’s Fast Track pathway and rolling review. Initial CMC and nonclinical modules are in, with the clinical section planned for the second quarter of 2026.

The filing follows the Phase 3 SHIELD II trial, where D-PLEX₁₀₀ delivered a 60% relative risk reduction in infection incidence with strong statistical support (p=0.0013). The product also holds FDA Breakthrough Therapy Designation, signaling the agency views the indication and data as potentially addressing a serious unmet need.

Management highlights ongoing talks for a U.S. commercialization partnership, which, if finalized, could shape launch execution once regulatory review is complete. Future company disclosures will need to clarify NDA acceptance status, review milestones and any partnership terms that emerge.

Key Figures

NDA timing: Clinical section in Q2 2026 Risk reduction in SSIs: 60% relative risk reduction Statistical significance: p=0.0013 +1 more

4 metrics

NDA timing Clinical section in Q2 2026 Additional NDA components expected to be submitted in the second quarter of 2026

Risk reduction in SSIs 60% relative risk reduction Phase 3 SHIELD II trial after abdominal colorectal surgery

Statistical significance p=0.0013 Efficacy of D-PLEX100 in reducing surgical site infections in SHIELD II

Duration of local drug release 30 days Period of prolonged doxycycline release at surgical site using Kynatrix technology

Key Terms

New Drug Application, Fast Track designation, rolling review, Breakthrough Therapy Designation, +2 more

6 terms

New Drug Application regulatory

"announced that it has initiated a New Drug Application (“NDA”) submission to the U.S. Food and Drug Administration"

A new drug application is a formal request submitted to government regulators seeking approval to market a new medicine. It is like a detailed proposal that shows the drug has been tested for safety and effectiveness. For investors, receiving approval signals that the drug may soon become available for sale, potentially leading to revenue growth and impacting the company's value.

Fast Track designation regulatory

"The NDA is being submitted under the FDA’s Fast Track designation, which allows for rolling review."

Fast track designation is a status the U.S. Food and Drug Administration grants to drugs intended to treat serious conditions and address an unmet medical need. It gives the developer more frequent communication with the FDA and can allow parts of the application to be reviewed on a rolling basis, and it may pave the way to priority review or accelerated approval. It can shorten development timelines, though it does not guarantee approval.

rolling review regulatory

"The NDA is being submitted under the FDA’s Fast Track designation, which allows for rolling review."

A rolling review is a regulatory process where health authorities examine data on a drug or vaccine as it becomes available instead of waiting for a complete file at the end. For investors, this can speed up the timeline to approval and reduce uncertainty because regulators assess progress in real time—think of reading and approving chapters of a book as they’re finished rather than waiting for the whole manuscript, which can bring forward potential market access and revenue.

Breakthrough Therapy Designation regulatory

"D-PLEX100 received Breakthrough Therapy Designation from the FDA for the prevention of SSIs"

A breakthrough therapy designation is a regulatory fast-track given to a drug or treatment that shows early signs of providing a major improvement over existing options for a serious condition. Think of it as a VIP lane that can speed up development and more intensive guidance from regulators, which matters to investors because it can shorten time to market, reduce development risk and potentially increase a company’s value — though it does not guarantee approval.

surgical site infections medical

"for D-PLEX100 for the prevention of surgical site infections (“SSIs”) in patients undergoing colorectal surgery."

Surgical site infections are infections that occur where a surgical cut was made, caused by bacteria or other germs entering the wound during or after an operation. They matter to investors because higher infection rates can increase hospital costs, lead to regulatory action, product recalls, lawsuits, and damaged reputations—similar to how a manufacturing defect forces costly recalls and repairs—so they affect revenue, margins, and risk for companies in healthcare and medical products.

Phase 3 SHIELD II trial medical

"D-PLEX100 recently demonstrated positive results in the Phase 3 SHIELD II trial, achieving a statistically significant 60% relative risk reduction"

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did PolyPid (PYPD) announce regarding D-PLEX100 and the FDA?

PolyPid announced it has begun a New Drug Application submission to the U.S. FDA for D-PLEX100. The drug targets prevention of surgical site infections in colorectal surgery and is being submitted under Fast Track designation with a rolling review process.

What is D-PLEX100 and what did the Phase 3 SHIELD II trial show?

D-PLEX100 is a locally applied, controlled-release doxycycline formulation designed to prevent surgical site infections. In the Phase 3 SHIELD II trial, it achieved a statistically significant 60% relative risk reduction in infection incidence after abdominal colorectal surgery, with a p-value of 0.0013.

How is PolyPid submitting the D-PLEX100 NDA and what is the expected timing?

PolyPid is using the FDA’s Fast Track pathway, allowing a rolling NDA review. It has submitted Chemistry, Manufacturing and Controls and nonclinical sections, with the clinical section expected to be submitted in the second quarter of 2026, according to the company.

What FDA designations has D-PLEX100 received according to PolyPid’s filing?

D-PLEX100 has received FDA Breakthrough Therapy Designation for preventing surgical site infections in elective colorectal surgery. The NDA is also being submitted under Fast Track designation, which permits rolling review of different application modules by the agency.

What commercialization plans did PolyPid (PYPD) mention for D-PLEX100?

PolyPid stated it is highly focused on potential approval and commercialization of D-PLEX100 and that negotiations for a U.S. commercialization partnership are on track. These discussions aim to support market entry if the FDA ultimately approves the product.

How does D-PLEX100 work to prevent surgical site infections?

D-PLEX100 uses PolyPid’s Kynatrix technology to pair with active pharmaceutical ingredients and deliver doxycycline directly at the surgical site. It provides prolonged, continuous antibiotic release over 30 days, aiming to maintain high local drug concentrations and reduce infection risk, including from resistant bacteria.

AI-generated analysis. How Rhea-AI works. Not financial advice.

Form 6-K: How Foreign Companies Report to the SEC →

See more from StockTitan in Google Search and AI answers. Adds StockTitan as a preferred source · opens Google

Add on Google Not now

Accepted by SEC EDGAR 03/31/2026 - 08:35 AM Learn about SEC filing dates

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 6-K

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the Month of: March 2026

Commission File Number: 001-38428

PolyPid Ltd.

(Translation of registrant’s name into English)

18 Hasivim Street

Petach Tikva 495376, Israel

(Address of principal executive office)

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:

☒ Form 20-F     ☐ Form 40-F

CONTENTS

Attached hereto and incorporated herein is PolyPid Ltd.’s (the “Registrant”) press release issued on March 31, 2026, titled “PolyPid Initiates D-PLEX₁₀₀ NDA Submission to the FDA.”

The first two paragraphs and the section titled “Forward-Looking Statements” in the press release are incorporated by reference into the Registrant’s registration statements on Form F-3 (File No. 333-276826, File No. 333-280658, File No. 333-281863, File No. 333-284376 and File No. 333-289034)  and Form S-8 (File No. 333-239517, File No. 333-271060, File No. 333-277703, File No. 333-280662 and File No. 333-289570) filed  with the Securities and Exchange Commission to be a part thereof from the date on which this report is submitted, to the extent not superseded by documents or reports subsequently filed or furnished. 

1

EXHIBIT INDEX

Exhibit No.
99.1		Press Release issued by PolyPid Ltd. on March 31, 2026, titled “PolyPid Initiates D-PLEX₁₀₀ NDA Submission to the FDA.”

2

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

	POLYPID LTD.
Date: March 31, 2026	By:	/s/ Jonny Missulawin
		Name:	Jonny Missulawin
		Title:	Chief Financial Officer

3

Exhibit 99.1

PolyPid Initiates D-PLEX₁₀₀ NDA Submission to the FDA

PolyPid Submits First Modules as Part of Rolling NDA Review; Completion expected in Second Quarter of 2026

U.S. Commercialization Partnership Negotiations on Track

PETACH TIKVA, Israel, March 31, 2026 (GLOBE NEWSWIRE) -- PolyPid Ltd. (Nasdaq: PYPD) (“PolyPid” or the “Company”), an innovative biopharmaceutical company dedicated to improving patient outcomes by elevating treatment effectiveness, right where care begins, today announced that it has initiated a New Drug Application (“NDA”) submission to the U.S. Food and Drug Administration (the “FDA”) for D-PLEX₁₀₀ for the prevention of surgical site infections (“SSIs”) in patients undergoing colorectal surgery.

The NDA is being submitted under the FDA’s Fast Track designation, which allows for rolling review. The submission includes the Chemistry, Manufacturing and Controls (CMC) and nonclinical sections of the NDA, with additional components, including the clinical section, expected to be submitted in the second quarter of 2026.

“This submission marks a pivotal milestone for PolyPid as we advance D-PLEX₁₀₀ into its regulatory approval phase,” said Dikla Czaczkes Akselbrad, Chief Executive Officer of PolyPid. “Following the positive results from our successful Phase 3 SHIELD II trial and constructive feedback from our previously announced pre-NDA meeting with the FDA, we are pleased to initiate the NDA submission. We are highly focused on executing toward potential approval and commercialization, with the goal of bringing D-PLEX₁₀₀ to patients undergoing surgery, while advancing discussions for a U.S. commercialization partnership.”

About D-PLEX₁₀₀

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, PolyPid’s delivery technology, Kynatrix, 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 recently demonstrated positive results in the Phase 3 SHIELD II trial, achieving a statistically significant 60% (p= 0.0013) relative risk reduction in SSI incidence following abdominal colorectal surgery with large incisions. D-PLEX₁₀₀ received Breakthrough Therapy Designation from the FDA for the prevention of SSIs in patients undergoing elective colorectal surgery.

About PolyPid

PolyPid Ltd. (Nasdaq: PYPD) is an innovative biopharmaceutical company dedicated to elevating treatment effectiveness, right where care begins. The Company develops long-acting, controlled-release drugs designed to deliver therapy precisely at the site of care, addressing critical unmet medical needs across a wide and diverse pipeline spanning surgical care, metabolic diseases, and beyond. PolyPid’s lead product, D-PLEX₁₀₀, successfully met its primary and all key secondary endpoints in the landmark Phase 3 SHIELD II trial for the prevention of surgical site infections. Guided by a commitment to precision and innovation, PolyPid is redefining how therapies perform and raise the standard of patient care. For additional Company information, please visit http://www.polypid.com and follow us on Twitter (X) and LinkedIn.

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 progress of the rolling NDA submission for D-PLEX₁₀₀ and the expected timing thereof, the Company’s expectations regarding potential approval of D-PLEX₁₀₀, and potential commercial partnership for the U.S. market. 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 25, 2026. 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 statements. 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.

Company Contact:

PolyPid Ltd.
Ori Warshavsky
908-858-5995
IR@Polypid.com

Investor Relations Contact:

Arx Investor Relations
North American Equities Desk
polypid@arxhq.com

Filing Exhibits & Attachments

1 document

Press Releases

• EX-99.1 PRESS RELEASE ISSUED BY POLYPID LTD. ON MARCH 31, 2026, TITLED "POLYPID INITIATE 10.9 KB