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PolyPid Announces Publication in International Journal of Surgery Highlighting Results of Phase 3 SHIELD I Trial of D-PLEX₁₀₀ in Prevention of Surgical Site Infections in Abdominal Colorectal Surgery

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PolyPid (Nasdaq: PYPD) announced the publication of results from its Phase 3 SHIELD I trial of D-PLEX₁₀₀ in the International Journal of Surgery. The study, one of the largest Phase 3 trials in surgical site infection (SSI) prevention in colorectal resection in over a decade, did not meet its primary endpoint. However, pre-specified and post-hoc analyses suggested D-PLEX100 may benefit patients with increased SSI risk, particularly those with lengthy incisions.

Key findings include:

  • 23% event reduction in the D-PLEX100 arm (not statistically significant)
  • 54% reduction in primary outcome events for incisions >20 cm (statistically significant)
  • 54.6% reduction in incisional SSI for incisions >20 cm
  • No safety concerns raised

The ongoing SHIELD II study focuses on patients with large surgical incisions, with top-line results expected in Q1 2025.

PolyPid (Nasdaq: PYPD) ha annunciato la pubblicazione dei risultati del suo studio di Fase 3 SHIELD I relativo a D-PLEX₁₀₀ nella rivista International Journal of Surgery. Lo studio, uno dei più grandi dell'ultimo decennio sulla prevenzione delle infezioni del sito chirurgico (SSI) nella resezione colorettale, non ha raggiunto l'endpoint primario. Tuttavia, le analisi predefinite e post-hoc suggeriscono che D-PLEX100 potrebbe beneficiare i pazienti a rischio elevato di SSI, in particolare quelli con incisioni ampie.

I risultati chiave includono:

  • Riduzione del 23% degli eventi nel braccio D-PLEX100 (non statisticamente significativa)
  • Riduzione del 54% degli eventi riguardanti l'esito primario per incisioni >20 cm (statisticamente significativa)
  • Riduzione del 54,6% delle SSI incisionale per incisioni >20 cm
  • Nessuna preoccupazione per la sicurezza sollevata

Lo studio SHIELD II in corso si concentra su pazienti con ampie incisioni chirurgiche, con risultati preliminari attesi nel primo trimestre del 2025.

PolyPid (Nasdaq: PYPD) anunció la publicación de los resultados de su ensayo de Fase 3 SHIELD I sobre D-PLEX₁₀₀ en la International Journal of Surgery. El estudio, uno de los más grandes ensayos de Fase 3 en prevención de infecciones del sitio quirúrgico (SSI) en resecciones colorrectales en más de una década, no alcanzó su objetivo primario. Sin embargo, los análisis predefinidos y post-hoc sugirieron que D-PLEX100 podría beneficiar a los pacientes con alto riesgo de SSI, particularmente aquellos con incisiones largas.

Los hallazgos clave incluyen:

  • Reducción del 23% en el grupo de D-PLEX100 (no estadísticamente significativa)
  • Reducción del 54% en eventos del resultado primario para incisiones >20 cm (estadísticamente significativa)
  • Reducción del 54.6% en SSI incisional para incisiones >20 cm
  • No se plantearon preocupaciones de seguridad

El estudio SHIELD II en curso se centra en pacientes con grandes incisiones quirúrgicas, con resultados preliminares esperados en el primer trimestre de 2025.

PolyPid (Nasdaq: PYPD)는 International Journal of Surgery에 D-PLEX₁₀₀에 대한 3상 SHIELD I 시험 결과를 발표했다고 밝혔습니다. 이번 연구는 지난 10년간 대장 절제술에서 수술 부위 감염(SSI) 예방에 관한 가장 큰 3상 시험 중 하나였으나 주요 종료 목표를 달성하지 못했습니다. 그러나 미리 정해진 분석과 후속 분석에 따르면 D-PLEX100은 특히 길이가 긴 절개 부위가 있는 SSI 위험이 높은 환자에게 이익이 될 수 있습니다.

주요 발견 사항은 다음과 같습니다:

  • D-PLEX100 그룹에서 23%의 사건 감소(통계적으로 유의미하지 않음)
  • 절개가 >20 cm인 경우 주 결과 이벤트에서 54% 감소(통계적으로 유의미함)
  • 절개가 >20 cm인 경우 SSI 절개에서 54.6% 감소
  • 안전성 문제 없음

PolyPid (Nasdaq: PYPD) a annoncé la publication des résultats de son essai de Phase 3 SHIELD I sur D-PLEX₁₀₀ dans le International Journal of Surgery. L'étude, l'un des plus grands essais de Phase 3 sur la prévention des infections du site opératoire (SSI) lors de la résection colorectale depuis plus d'une décennie, n'a pas atteint son objectif principal. Cependant, les analyses préétablies et post-hoc ont suggéré que D-PLEX100 pourrait bénéficier aux patients présentant un risque accru de SSI, en particulier ceux ayant des incisions longues.

Les résultats clés incluent :

  • Réduction de 23 % des événements dans le groupe D-PLEX100 (non statistiquement significatif)
  • Réduction de 54 % des événements concernant le résultat principal pour des incisions >20 cm (statistiquement significatif)
  • Réduction de 54,6 % des SSI incisionnelles pour des incisions >20 cm
  • Aucun problème de sécurité soulevé

L'étude SHIELD II en cours se concentre sur les patients ayant de grandes incisions chirurgicales, avec des résultats préliminaires attendus au premier trimestre de 2025.

PolyPid (Nasdaq: PYPD) hat die Veröffentlichung der Ergebnisse seiner Phase 3-Studie SHIELD I zu D-PLEX₁₀₀ im International Journal of Surgery bekannt gegeben. Die Studie, eine der größten Phase 3-Studien zur Prävention von Wundinfektionen (SSI) bei kolorektalen Resektionen in über einem Jahrzehnt, erreichte nicht den primären Endpunkt. Allerdings deuteten vordefinierte und nachträgliche Analysen darauf hin, dass D-PLEX100 Patienten mit erhöhtem SSI-Risiko, insbesondere solche mit langen Einschnitten, zugutekommen könnte.

Wichtige Ergebnisse sind:

  • 23% Reduzierung der Ereignisse in der D-PLEX100-Gruppe (nicht statistisch signifikant)
  • 54% Reduzierung der primären Ergebnisevents für Einschnitte >20 cm (statistisch signifikant)
  • 54,6% Reduzierung der SSI bei Einschnitten >20 cm
  • Keine Sicherheitsbedenken geäußert

Die laufende SHIELD II-Studie konzentriert sich auf Patienten mit großen chirurgischen Einschnitten, wobei die Ergebnisse im ersten Quartal 2025 erwartet werden.

Positive
  • 54% statistically significant reduction in primary outcome events for incisions >20 cm
  • 54.6% reduction in incisional SSI for incisions >20 cm
  • No safety concerns raised by the independent Data Safety Monitoring Board
  • Ongoing SHIELD II study focusing on patients with large surgical incisions
Negative
  • SHIELD I study did not meet its primary endpoint
  • Overall 23% event reduction in D-PLEX100 arm was not statistically significant
  • COVID-19 safety restrictions impacted overall infection rate, making primary outcome difficult to meet

Insights

The publication of SHIELD I trial results in the International Journal of Surgery is significant for PolyPid, offering valuable insights into D-PLEX100's potential in preventing surgical site infections (SSIs). While the study didn't meet its primary endpoint, likely due to COVID-19 impacts, it revealed promising data for high-risk patients:

  • 54% reduction in primary outcome events for patients with incisions >20 cm (p=0.0032)
  • 54.6% reduction in incisional SSIs for the same subgroup (p=0.0410)
  • 54.6% decrease in need for surgical reintervention (p=0.0333)

These results suggest D-PLEX100 could be particularly beneficial for patients with longer incisions or multiple risk factors. The ongoing SHIELD II study, focusing on patients with large surgical incisions, may provide more definitive evidence. With top-line results expected in Q1 2025, this could be a pivotal moment for PolyPid in addressing the significant unmet need in SSI prevention.

While the SHIELD I results are encouraging for certain patient subgroups, the overall impact on PolyPid's financial outlook remains uncertain. Key considerations include:

  • The ongoing SHIELD II study is important for potential FDA approval and market entry
  • If successful, D-PLEX100 could address a substantial market, given the high cost of SSIs to commercial payers
  • However, the 24.4 million market cap suggests investor caution

The upcoming unblinded interim analysis of SHIELD II later this quarter could be a significant catalyst. Positive results might boost investor confidence and potentially lead to partnerships or increased funding. Conversely, negative results could pose significant challenges for this small-cap company. Investors should closely monitor the SHIELD II progress, as it will likely have a substantial impact on PolyPid's valuation and future prospects.

SHIELD I Study is One of the Largest Phase 3 Trials in the Prevention of SSIs in Colorectal Resection Conducted in Over a Decade

Pre-Specified and Post-Hoc Analyses Suggested that D-PLEX100 May Benefit Patients with Increased SSI Risk, Including Those with Lengthy Incisions

SHIELD II Study, the Ongoing Second Phase 3 with D-PLEX100, Focuses on Patients with Large Surgical Incisions; Top-line Results Expected in Q1 2025

PETACH TIKVA, Israel, Oct. 21, 2024 (GLOBE NEWSWIRE) -- PolyPid Ltd. (Nasdaq: PYPD) (“PolyPid” or the “Company”), a late-stage biopharma company aiming to improve surgical outcomes, today announced a publication in the International Journal of Surgery (IJS) titled, "Effect of Local Prolonged-Release Incisional Doxycycline on Surgical Site Infection Prophylaxis in Abdominal Colorectal Surgery: The SHIELD I Randomized Clinical Trial.” The article highlights the full dataset from the first Phase 3 study (NCT04233424) of D-PLEX100, from which top-line results were announced in September 2022.

“The overall infection rate in SHIELD I was significantly impacted by the COVID-19-related safety restrictions introduced in the surgical setting during the pandemic,” said Prof. Oded Zmora, Professor of Surgery at the Shamir Medical Center in Tel Aviv Israel, and President of the European Society of Coloproctology. “Given this unexpected change in baseline infection rate, the SHIELD I primary outcome became extraordinarily difficult to meet. For this reason, while the SHIELD I study did not achieve its primary endpoint, both pre-specified and post-hoc analyses suggested that D-PLEX100 may benefit patients at increased risk of surgical site infections (SSIs), including those with lengthy incisions. While SHIELD II is ongoing, the clinical data generated by D-PLEX100 to date suggest it may be a promising future adjunctive component of surgical care bundles.”

A virtual KOL event hosted by the Company in June 2024, highlighted that procedural and patient-related risk factors, such as smoking, alcohol abuse, type 2 diabetes and a high BMI, are known to have a significant negative impact on the risk of developing an SSI, and this increase in risk is compounded when patients have multiple risk factors. During the presentation, Prof. Charles E. Edmiston, Emeritus Professor of Surgery, Division of Vascular Surgery, Medical College of Wisconsin, also confirmed that the long-term cost of SSIs to commercial payers is substantial and concluded there remains a significant unmet need for additional measures that prevent the development of SSIs.

“We are thrilled to have the SHIELD I study results published in the highly regarded International Journal of Surgery, ranked second out of 212 titles in the Surgery category by impact factor1. Importantly, in the post-COVID-19 setting, we are seeing infection rates normalize to levels on par with those prior to the pandemic. We expect the SHIELD II infection rate to be more in line with the pre-pandemic rate and remain encouraged by the data generated in the SHIELD I pre-specified subgroup analysis that evaluated the primary endpoint in patients with incision lengths over 20 cm, which showed a 54% reduction in SSI rates between the D-PLEX100 treatment arm and the control arm,” said Dikla Czaczkes Akselbrad, PolyPid’s Chief Executive Officer. “Earlier this month, we enrolled the last patient required to conduct the planned SHIELD II unblinded interim analysis, which is anticipated to occur later this quarter and will be followed by the availability of top-line results, expected in the first quarter of 2025.”

Phase 3 SHIELD I Trial Results
The IJS article presents results of the Phase 3 SHIELD I trial (Surgical site Hospital acquired Infection prEvention with Local D-PLEX), 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 included prophylactic systemic antibiotics, compared to a SoC alone arm, in prevention of post-abdominal surgery incisional infection. The primary endpoint of the trial was the combination of incisional SSIs, incisional reinterventions due to suspected SSI or to poor wound healing including wound dehiscence, as determined by a blinded and independent adjudication committee, and mortality for any reason within 30 days post-surgery. The trial enrolled 977 patients, with 488 in the D-PLEX100 arm and 489 in the SoC arm, from more than 60 centers in the United States, Europe and Israel.

  • A total of 104 patients experienced a primary outcome event: 45/485 (9.3%) in D-PLEX100 versus 59/489 (12.1%) in SoC. The clinically meaningful 23% event reduction in the D-PLEX100 treatment arm was not statistically significant (p=0.1520).
  • In the greater than 20 cm incision length pre-specified subgroup, a statistically significant 54% reduction in primary outcome events was observed in D-PLEX100 (8%, 17/212) compared with SoC (17.5%, 37/211, p=0.0032).
  • Analysis of the key secondary efficacy outcome, incisional SSI, also indicated a 54.6% reduction in the greater than 20 cm incision subgroup (4.4% in D-PLEX100 vs. 9.7% in SoC, p= 0.0410).
  • Exploratory analysis of the additional secondary efficacy outcomes indicated marked differences in favor of D-PLEX100 vs. SoC in the greater than 20 cm incision length subgroup. Notably, the need for any surgical reintervention decreased by 54.6% in the D-PLEX100 treatment arm compared to the SOC arm (4.4% vs. 9.7%, p= 0.0333).
  • There were no safety concerns raised by the independent Data Safety Monitoring Board in SHIELD I. The overall incidence of treatment emergent adverse events (TEAEs) was similar between the study arms, with numerically lower incidences of severe and serious TEAEs, and any TEAEs requiring surgical reinterventions in the D-PLEX100 arm compared to the SoC arm.

About SHIELD II
SHIELD II is a prospective, multinational, randomized, double blind Phase 3 trial designed to assess the efficacy and safety of D-PLEX100 administered concomitantly with SoC, which includes prophylactic systemic antibiotics, compared to SoC alone arm, in the prevention of post abdominal-surgery incisional infection in patients undergoing surgeries with incisions greater than 20 cm. The primary endpoint of the trial is measured by the proportion of subjects with either an 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.

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, 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.

About PolyPid
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 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 with glioblastoma.

For additional Company information, please visit http://www.polypid.com and follow us on Twitter 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 potential benefits and advantages of D-PLEX100, that D-PLEX100 may be a promising future adjunctive component of surgical care bundles, the Company’s expectation that the SHIELD II infection rate will be more in line with the pre-pandemic rates, total recruitment time into the SHIELD II study and the timing of the top-line results and an unblinded interim analysis. 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 (“SEC”), including, but not limited to, the risks detailed in the Company’s Annual Report on Form 20-F filed on March 6, 2024. 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.

Contacts:
PolyPid Ltd. 
Ori Warshavsky
COO – US
908-858-5995
IR@Polypid.com

Investors:
Brian Ritchie
LifeSci Advisors
212-915-2578
BRitchie@lifesciadvisors.com


1 Based on OOIR.org https://ooir.org/journals.php?field=Clinical+Medicine&category=Surgery&metric=jif 


FAQ

What were the main results of PolyPid's SHIELD I trial for D-PLEX100 (PYPD)?

The SHIELD I trial did not meet its primary endpoint, showing a 23% event reduction in the D-PLEX100 arm that was not statistically significant. However, for incisions >20 cm, there was a statistically significant 54% reduction in primary outcome events and a 54.6% reduction in incisional SSI.

When are the top-line results for PolyPid's SHIELD II trial expected (PYPD)?

The top-line results for PolyPid's SHIELD II trial of D-PLEX100 are expected in the first quarter of 2025.

What is the focus of PolyPid's ongoing SHIELD II study for D-PLEX100 (PYPD)?

The ongoing SHIELD II study focuses on patients with large surgical incisions, based on the promising results seen in this subgroup from the SHIELD I trial.

Were there any safety concerns in PolyPid's SHIELD I trial for D-PLEX100 (PYPD)?

No safety concerns were raised by the independent Data Safety Monitoring Board in the SHIELD I trial. The overall incidence of treatment emergent adverse events was similar between study arms.

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