PYPD D-PLEX100

Surgical site infection prevention · PolyPid · NDA

Of 100 applications in this same position, about 70 get approved.

Until the FDA deadline53d

Base rate76%

Gap−6pts

PDUFA target date 2026-11-28the FDA may act earlier or later

Summary

FDA approval of D-PLEX100 in this review cycle is put at 70%, below the 76% base rate for first-time applications from smaller companies. The clinical case is solid: the pivotal SHIELD II trial cut a composite of wound infection, re-intervention and death from 18.1% to 10.9% (p=0.0039), on a design FDA agreed in advance. Manufacturing holds the estimate down. This is PolyPid's first product, made in its own sterile plant in Israel, which FDA has never cleared, and there is no public record that the pre-approval inspection has happened. Lesser concerns: an earlier Phase 3 trial failed, only 4 of 975 patients were enrolled in the United States, and wound dehiscence was more frequent with the drug.

Recorded 2026-10-05 08:21 UTC · v1Proof ↓

Evidence · 10 items

Why 70%, not 76%

Indication

Prevention of surgical site infections in patients undergoing abdominal colorectal surgery (the pivotal trial enrolled patients with incisions longer than 20 cm)

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▲ SupportsMedium The pivotal trial met its primary endpoint and all three key secondary endpoints

SHIELD II was a randomized Phase 3 trial of D-PLEX100 added to standard care versus standard care alone in elective colorectal resection; the primary analysis covered patients with an incision longer than 20 cm (405 versus 393). The primary endpoint, a composite of incisional infection, re-intervention at the incision or death from any cause within 30 days, occurred in 10.9% (95% CI 8.0 to 14.3) versus 18.1% (95% CI 14.4 to 22.2), a difference of -7.2 percentage points (95% CI -12.1 to -2.3; p=0.0039). Incisional infection alone, judged by a blinded independent committee, was 3.8% versus 9.5% (difference -5.8 points, 95% CI -9.3 to -2.3; p=0.0013). The composite in all 975 randomized patients (incisions over 7 cm) was 11.1% versus 17.4% (p=0.0047), and the share of patients with an ASEPSIS wound score above 20 was 2.0% versus 5.6% (p=0.0103). There is no public record of a peer-reviewed publication of SHIELD II as of 5 October 2026; the figures are the sponsor's entries in the trial registry.

Source: ClinicalTrials.gov NCT04411199 (SHIELD II), results first posted 2026-07-13: https://clinicaltrials.gov/study/NCT04411199?tab=results; PolyPid 6-K exhibit 99.1, 2025-06-09 (SHIELD II topline): https://www.sec.gov/Archives/edgar/data/1611842/000121390025052320/ea024508901ex99-1_polypid.htm
02▲ SupportsSmall FDA shaped the trial and agreed in advance that one pivotal trial could be enough

By the company's account: in May 2021 FDA agreed in a Type B meeting that a single pivotal Phase 3 study would be sufficient for approval in colorectal surgery, provided the results were adequate; in January 2023, after the first Phase 3 trial, FDA said its large-incision results "may provide supportive evidence" and recommended one additional study, a role SHIELD II could fill; in May 2023 FDA agreed to the revised SHIELD II design; and in the pre-NDA minutes announced on 3 December 2025 FDA agreed that the clinical package "appears adequate to support NDA submission and review". The large-incision analysis of the first trial had itself been requested by FDA. D-PLEX100 holds Breakthrough Therapy designation (November 2020), Fast Track status and three Qualified Infectious Disease Product designations. In February 2026 FDA's leadership wrote that one adequate and well-controlled trial plus confirmatory evidence is now the default basis for approval. Limits: none of FDA's letters or minutes is public, and the pre-NDA wording is about whether the package can be submitted and reviewed, not whether it will be approved.

Source: PolyPid 20-F for FY2024, filed 2025-02-26: https://www.sec.gov/Archives/edgar/data/1611842/000121390025017412/ea0231533-20f_polypid.htm; PolyPid 6-K exhibit 99.1, 2023-01-24 (FDA Type D feedback): https://www.sec.gov/Archives/edgar/data/1611842/000121390023004609/ea172110ex99-1_polypid.htm; PolyPid 6-K exhibit 99.1, 2025-12-03 (pre-NDA minutes): https://www.sec.gov/Archives/edgar/data/1611842/000121390025117581/ea026831301ex99-1_polypid.htm; PolyPid 20-F for FY2025, filed 2026-02-25: https://www.sec.gov/Archives/edgar/data/1611842/000121390026020370/ea0276727-20f_polypid.htm; Prasad and Makary, N Engl J Med 2026;394(8):815-7, as summarised by AMR.Solutions on 2026-03-01: https://amr.solutions/2026/03/01/fda-one-pivotal-trial-confirmatory-evidence-is-default-expectation-for-approval/
03▲ SupportsSmall The application was filed with no review issues flagged, and no advisory committee has been called

PolyPid announced on 1 June 2026 that its rolling submission was complete. FDA accepted the application for filing on 27 July 2026 and, according to the company, "did not identify any filing review issues". The goal date of 28 November 2026 follows from priority review, but that status says little about FDA's view of the data: the law requires priority review for the first application for a product with Qualified Infectious Disease Product designation. The company has announced no advisory committee meeting on the application, and the Federal Register carries no meeting notice for the Antimicrobial Drugs Advisory Committee since June 2026. On 12 August 2026 the chief executive described the review as effective and efficient, with several rounds of communication with FDA. No mid-cycle or late-cycle meeting outcome and no labeling discussion has been disclosed. 28 November 2026 is a Saturday, two days after Thanksgiving, so FDA may act a few days earlier.

Source: PolyPid 6-K exhibit 99.1, 2026-06-01 (submission completed): https://www.sec.gov/Archives/edgar/data/1611842/000121390026063169/ea029288201ex99-1.htm; PolyPid 6-K exhibit 99.1, 2026-07-29 (FDA acceptance): https://www.sec.gov/Archives/edgar/data/1611842/000121390026082564/ea029964201ex99-1.htm; PolyPid 6-K exhibit 99.1, 2026-08-12 (Q2 2026 update): https://www.sec.gov/Archives/edgar/data/1611842/000121390026088040/ea030152801ex99-1.htm; FDA guidance, Qualified Infectious Disease Product Designation Questions and Answers: https://www.fda.gov/media/148480/download; Federal Register, notices mentioning the Antimicrobial Drugs Advisory Committee, searched 2026-10-05: https://www.federalregister.gov/documents/search?conditions%5Bterm%5D=%22Antimicrobial+Drugs+Advisory+Committee%22; PolyPid Q2 2026 results call transcript, 2026-08-12: https://www.fool.com/earnings/call-transcripts/2026/08/19/polypid-pypd-q2-2026-earnings-call-transcript/
04▼ AgainstSmall An earlier Phase 3 trial failed, and the successful one tests a subgroup taken from it

The first Phase 3 trial, SHIELD I (977 patients, incisions over 10 cm), missed its primary endpoint in September 2022: 9.3% versus 12.1% (difference -2.8 points, 95% CI -6.7 to 1.0; p=0.152), with incisional infection at 6.2% versus 6.9% (p=0.62). In a pre-specified analysis of the 423 patients with incisions over 20 cm, not adjusted for multiple testing, the primary endpoint occurred in 17 of 212 (8.0%) versus 37 of 211 (17.5%), p=0.0032. SHIELD II had by then enrolled more than 200 patients under broader criteria, about 40 of them with large incisions; in 2023 it was re-designed to enrol only incisions over 20 cm. Testing a subgroup result in a new prospective trial is the accepted way to confirm it, and the result repeated. Even so, the package is one successful trial and one failed trial, with a primary p-value of 0.0039. SHIELD II also had an unblinded interim analysis of the first 430 patients, after which the sample was raised from a minimum of 624 to 800. The control arm received no placebo and the surgical team knew the assignment; wound assessors and the adjudication committee were blinded. The company's annual report for 2025, unlike the one for 2024, no longer describes the first trial.

Source: ClinicalTrials.gov NCT04233424 (SHIELD I), results first posted 2025-06-22: https://clinicaltrials.gov/study/NCT04233424?tab=results; PolyPid 6-K exhibit 99.1, 2022-09-02 (SHIELD I topline): https://www.sec.gov/Archives/edgar/data/1611842/000121390022053474/ea165323ex99-1_polypid.htm; Zmora et al., SHIELD 1 randomized clinical trial, International Journal of Surgery 2024: https://pmc.ncbi.nlm.nih.gov/articles/PMC11486998/; PolyPid 20-F for FY2024, filed 2025-02-26: https://www.sec.gov/Archives/edgar/data/1611842/000121390025017412/ea0231533-20f_polypid.htm; PolyPid 6-K exhibit 99.1, 2024-12-26 (interim analysis): https://www.sec.gov/Archives/edgar/data/1611842/000121390024112468/ea022575301ex99-1_polypid.htm; ClinicalTrials.gov NCT04411199 (SHIELD II), results first posted 2026-07-13: https://clinicaltrials.gov/study/NCT04411199?tab=results; PolyPid 20-F for FY2025, filed 2026-02-25: https://www.sec.gov/Archives/edgar/data/1611842/000121390026020370/ea0276727-20f_polypid.htm
05▼ AgainstSmall Almost none of the pivotal-trial patients were treated in the United States

Of the 975 patients randomized in SHIELD II, 4 were enrolled in the United States. The largest contributors were Moldova (246), Hungary (181), Serbia (135), North Macedonia (113), Romania (104), Bosnia and Herzegovina (68) and Israel (55); 973 of the 975 were White. SHIELD I had 37 US patients out of 977. FDA's rule for applications that rest on foreign data asks that the data be applicable to the US population and US medical practice, and that FDA be able to validate them, by inspection where it sees the need. Randomization was stratified by region and by type of prophylaxis (including oral antibiotics with bowel preparation), but 4 US patients cannot give a US-specific estimate of the effect. On 2 September 2026 the directors of FDA's drug and biologics centers said the agency would step up inspections of trials run abroad. Against this, FDA knew where the patients had been enrolled when it accepted the application without filing issues. Whether FDA has inspected any trial site is not public.

Source: ClinicalTrials.gov NCT04411199 (SHIELD II), results first posted 2026-07-13: https://clinicaltrials.gov/study/NCT04411199?tab=results; ClinicalTrials.gov NCT04233424 (SHIELD I), results first posted 2025-06-22: https://clinicaltrials.gov/study/NCT04233424?tab=results; 21 CFR 314.106, foreign data: https://www.ecfr.gov/current/title-21/section-314.106; Hogan Lovells, 2026-09-16, on FDA's statement of 2026-09-02 about trials outside the US: https://www.hlc.com/en/publications/fda-signals-more-inspections-scrutiny-of-clinical-trials-outside-the-us; PolyPid 6-K exhibit 99.1, 2026-07-29 (FDA acceptance): https://www.sec.gov/Archives/edgar/data/1611842/000121390026082564/ea029964201ex99-1.htm
06▲ SupportsSmall No excess of serious harm, and fewer deaths, with D-PLEX100

In the SHIELD II safety population (481 on D-PLEX100, 493 on standard care, followed for 60 days) there were 10 deaths (2.1%) versus 19 (3.9%), and serious adverse events in 75 patients (15.6%) versus 85 (17.2%); serious postoperative wound infection was reported in 3 versus 10. In SHIELD I deaths were 16 of 485 versus 17 of 489 and serious adverse events 69 of 478 versus 98 of 498. The active ingredient, doxycycline, has long been approved, and the application relies in part on FDA's earlier findings for it (the 505(b)(2) route). Each 5 g vial holds 54.6 mg of doxycycline and at most three vials are used (163.8 mg); the company reports minimal systemic exposure.

Source: ClinicalTrials.gov NCT04411199 (SHIELD II), results first posted 2026-07-13: https://clinicaltrials.gov/study/NCT04411199?tab=results; ClinicalTrials.gov NCT04233424 (SHIELD I), results first posted 2025-06-22: https://clinicaltrials.gov/study/NCT04233424?tab=results; Zmora et al., SHIELD 1 randomized clinical trial, International Journal of Surgery 2024: https://pmc.ncbi.nlm.nih.gov/articles/PMC11486998/; PolyPid 20-F for FY2025, filed 2026-02-25: https://www.sec.gov/Archives/edgar/data/1611842/000121390026020370/ea0276727-20f_polypid.htm; PolyPid 6-K exhibit 99.1, 2026-05-13 (Q1 2026 update): https://www.sec.gov/Archives/edgar/data/1611842/000121390026055449/ea029031501ex99-1.htm
07▼ AgainstSmall Wound dehiscence was reported more often with D-PLEX100

In SHIELD II, non-serious wound dehiscence was reported in 25 of 481 patients (5.2%) on D-PLEX100 versus 8 of 493 (1.6%) on standard care; incision-site erythema in 65 versus 46 and swelling in 58 versus 45. Serious wound dehiscence (2 versus 2) and wound evisceration (2 versus 2) were balanced. In SHIELD I, impaired healing was reported in 7 of 478 versus 1 of 498, and wound dehiscence in 6 versus 5. The product leaves coated beta-tricalcium phosphate particles in the closed wound. This looks more like a matter for the label than a ground for rejection, and the company describes the safety profile as good, but FDA's reading of it is not public. FDA told the company in 2023 that a product for preventing infection has the potential for wide use.

Source: ClinicalTrials.gov NCT04411199 (SHIELD II), results first posted 2026-07-13: https://clinicaltrials.gov/study/NCT04411199?tab=results; ClinicalTrials.gov NCT04233424 (SHIELD I), results first posted 2025-06-22: https://clinicaltrials.gov/study/NCT04233424?tab=results; Zmora et al., SHIELD 1 randomized clinical trial, International Journal of Surgery 2024: https://pmc.ncbi.nlm.nih.gov/articles/PMC11486998/; PolyPid 6-K exhibit 99.1, 2023-01-24 (FDA Type D feedback): https://www.sec.gov/Archives/edgar/data/1611842/000121390023004609/ea172110ex99-1_polypid.htm
08▼ AgainstLarge First commercial product, made in the company's own sterile plant, which FDA has never cleared

PolyPid has no approved product. D-PLEX100, a sterile powder that is mixed into a paste at the time of surgery, is made at the company's leased plant of about 22,000 square feet in Petah Tikva, Israel. The license agreement of 17 July 2026 states that PolyPid is "currently only licensed by the Israeli Governmental Authorities for Manufacture of investigational medicinal product" and holds no FDA authorization for commercial supply; the annual report says the plant must pass an FDA pre-approval inspection before approval. On 12 August 2026 the chief executive said FDA had been in contact about the audits expected during the review, declined to give dates, and said the company had run several mock inspections with outside consultants. As of 5 October 2026 there is no public record that the inspection has taken place, or of its outcome. The six-month priority clock leaves little time to answer inspection findings before 28 November. A regional war with Iran ran from 28 February 2026 until a deal announced on 14 June 2026, while the application was being submitted, and the annual report warns that hostilities can disrupt operations. The doxycycline supplier and any contract manufacturers are not named in public filings, and the company says it relies on a sole supplier for several raw materials.

Source: PolyPid 20-F for FY2025, filed 2026-02-25: https://www.sec.gov/Archives/edgar/data/1611842/000121390026020370/ea0276727-20f_polypid.htm; License and Supply Agreement with Azurity dated 2026-07-17, exhibit 10.1 to the 6-K of 2026-07-21: https://www.sec.gov/Archives/edgar/data/1611842/000121390026079808/ea029855901ex10-1.htm; PolyPid management's discussion for the six months to 2026-06-30, 6-K exhibit 99.2, 2026-08-12: https://www.sec.gov/Archives/edgar/data/1611842/000121390026088439/ea030023101ex99-2.htm; PolyPid Q2 2026 results call transcript, 2026-08-12: https://www.fool.com/earnings/call-transcripts/2026/08/19/polypid-pypd-q2-2026-earnings-call-transcript/; PolyPid at the Lytham Partners investor conference, 2026-09-29 (transcript summary): https://www.investing.com/news/transcripts/polypid-at-lytham-partners-fda-decision-nears-for-lead-drug-93CH-4923807; Al Jazeera, 2026-06-15: https://www.aljazeera.com/news/2026/6/15/iran-us-agree-tentative-deal-to-end-war-your-questions-answered
09▲ SupportsSmall The plant has a clean record with Israel's regulator, and the process was validated in 2023

Israel's Ministry of Health completed a GMP audit of the plant in September 2023 "without any critical or major findings" and another in September 2025, which the company calls the fourth consecutive successful inspection; the audits are recognised in the EU under the EU-Israel conformity agreement. Three process-validation batches were completed in September 2023 and placed on stability testing. The manufacturing and nonclinical sections of the application went in first, on 30 March 2026, about two months before the clinical sections, giving FDA more time with them. Prospective commercial partners, including Azurity, carried out on-site diligence at the plant, according to management. Pre-launch inventory stood at $1.4 million on 30 June 2026. An Israeli GMP certificate does not replace an FDA inspection.

Source: PolyPid 20-F for FY2025, filed 2026-02-25: https://www.sec.gov/Archives/edgar/data/1611842/000121390026020370/ea0276727-20f_polypid.htm; PolyPid 20-F for FY2024, filed 2025-02-26: https://www.sec.gov/Archives/edgar/data/1611842/000121390025017412/ea0231533-20f_polypid.htm; PolyPid 6-K exhibit 99.1, 2025-09-16 (Israeli GMP inspection): https://www.sec.gov/Archives/edgar/data/1611842/000121390025087942/ea025753001ex99-1_polypid.htm; PolyPid 6-K exhibit 99.1, 2026-05-13 (Q1 2026 update): https://www.sec.gov/Archives/edgar/data/1611842/000121390026055449/ea029031501ex99-1.htm; PolyPid Q2 2026 results call transcript, 2026-08-12: https://www.fool.com/earnings/call-transcripts/2026/08/19/polypid-pypd-q2-2026-earnings-call-transcript/; PolyPid 6-K exhibit 99.1, 2026-08-12 (Q2 2026 update): https://www.sec.gov/Archives/edgar/data/1611842/000121390026088040/ea030152801ex99-1.htm
10▲ SupportsSmall A commercial partner paid $30 million before the decision, and launch is being prepared

On 17 July 2026 Azurity Pharmaceuticals took US and Canadian rights, paying $15 million on signing and a further $15 million once FDA accepted the application; up to about $300 million more depends on regulatory, development and sales milestones, and a US launch is targeted for early 2027. Management says Azurity is building the sales force and that joint launch teams are at work. PolyPid filed its European application on 14 September 2026, and the EMA has validated it. With the Azurity payments the company expects to fund operations into 2028, so the review does not coincide with a need to raise money. Insider filings since March 2026 show option grants only. On the other side, PolyPid and ADVANZ PHARMA ended their 2022 European license by mutual agreement, announced on 1 October 2026; the company presents this as a chance to find a new partner. The interim accounts to 30 June 2026 still carry a going-concern warning.

Source: PolyPid 6-K, 2026-07-21 (Azurity agreement): https://www.sec.gov/Archives/edgar/data/1611842/000121390026079808/ea0298559-6k_polypid.htm; PolyPid 6-K exhibit 99.1, 2026-08-12 (Q2 2026 update): https://www.sec.gov/Archives/edgar/data/1611842/000121390026088040/ea030152801ex99-1.htm; PolyPid Q2 2026 results call transcript, 2026-08-12: https://www.fool.com/earnings/call-transcripts/2026/08/19/polypid-pypd-q2-2026-earnings-call-transcript/; PolyPid 6-K exhibit 99.1, 2026-10-01 (EMA validation): https://www.sec.gov/Archives/edgar/data/1611842/000121390026105492/ea030731601ex99-1.htm; PolyPid 6-K exhibit 99.1, 2026-10-01 (ADVANZ termination): https://www.sec.gov/Archives/edgar/data/1611842/000121390026105474/ea030731501ex99-1.htm; PolyPid interim financial statements at 2026-06-30, 6-K exhibit 99.1, 2026-08-12: https://www.sec.gov/Archives/edgar/data/1611842/000121390026088439/ea030023101ex99-1.htm; SEC EDGAR filing list for PolyPid Ltd. (CIK 1611842), as of 2026-10-05: https://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001611842&type=&dateb=&owner=include&count=40

What would change this forecast

01
Up: PolyPid or FDA discloses that the pre-approval inspection of the Petah Tikva plant is complete with no observations, or with observations that FDA has accepted as resolved.
02
Up: the company reports labeling discussions or post-marketing commitments with FDA, the usual signs of a review heading towards approval.
03
Down: a Form 483 with significant observations at the plant or at a supplier, or word that the inspection cannot be completed before the goal date, including because of security conditions in Israel.
04
Down: FDA convenes an advisory committee, questions whether the Eastern European data apply to US practice, or reports data-integrity findings at high-enrolling trial sites.
05
Date change rather than a no: FDA extends the goal date after a major amendment; the estimate would then be reassessed against the new date.
06
Void rather than no: PolyPid withdraws the application before FDA acts.

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

Low

Manufacturing and inspection risk

High

D-PLEX100 is PolyPid's first commercial product and is made in the company's own sterile plant in Petah Tikva, Israel (about 22,000 square feet; the interim accounts call it a pilot manufacturing plant). The product is a complex formulation: a polymer-lipid matrix carrying doxycycline, coated on beta-tricalcium phosphate particles and supplied as a sterile powder in 5 g vials. As of July 2026 the plant was licensed by the Israeli authorities for investigational product only and had no FDA authorization for commercial supply; an FDA pre-approval inspection is required. In its favour: four consecutive successful GMP inspections by Israel's Ministry of Health (the latest in September 2025; the 2023 audit had no critical or major findings), three process-validation batches completed in September 2023, and manufacturing sections submitted two months ahead of the clinical ones. What cannot be judged: whether FDA has inspected the plant and with what result (no public record as of 5 October 2026); who supplies the doxycycline and the sole-sourced raw materials, and their inspection history; and how the packaging contractor chosen by Azurity fits into the application. The annual report also notes that an earlier Israeli audit of a contract manufacturer's process for D-PLEX100 produced critical observations, which the company says were resolved.

Record · version 1

Written on 2026-10-05, 54 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-05 08:21 UTC 70% Current version JSON ↓.ots ↓ ● Anchored in the Bitcoin blockchain

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Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-11-26. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.