PolyPid Ltd. (PYPD): Business Model Canvas [Dec-2025 Updated]

You're watching PolyPid Ltd. as they stand right on the edge of bringing their D-PLEX${}{\text{100}}$ product to market, which is a massive inflection point for any pre-commercial biotech. Honestly, the core value here is compelling: delivering localized, prolonged antibiotic release for a full 30 days to slash surgical site infections (SSIs) by a proven 58% relative risk reduction in colorectal surgery. Right now, the business model is all about securing that key U.S. commercialization partner while managing the final steps toward an NDA submission, all supported by $18.8 million in cash and equivalents as of September 30, 2025; so, let's break down exactly how PolyPid Ltd. plans to convert that clinical success into revenue streams below.

PolyPid Ltd. (PYPD) - Canvas Business Model: Key Partnerships

You're looking at the core external relationships PolyPid Ltd. needs to execute its commercialization plan for D-PLEX${ }{\text{100}}$. These aren't just vendors; they are essential gatekeepers and enablers for bringing their technology to market, especially given the company's current financial position.

The most immediate and tangible partnership validation comes from the regulatory and manufacturing side. PolyPid successfully completed its fourth consecutive Good Manufacturing Practice (GMP) inspection by the Israeli Ministry of Health (IMOH) on September 16, 2025. This is a big deal because it confirms their facility meets the standards required for commercial production, aligning with European regulatory standards under the EU-Israel Agreement on Conformity Assessment and Acceptance (ACAA) framework. This sets the stage for the next big hurdle.

That next hurdle is the U.S. Food and Drug Administration (FDA). PolyPid is on track for a New Drug Application (NDA) submission in early 2026. You should note that on December 3, 2025, the company announced supportive feedback from the FDA following a pre-NDA meeting, which confirmed the adequacy of their clinical data package and approved a rolling NDA review process. This de-risks the submission timeline, especially since D-PLEX${ }{\text{100}}$ already holds Fast Track and Breakthrough Therapy designations from the agency.

For the actual clinical execution, the costs associated with Contract Research Organizations (CROs) are reflected in the Research and Development (R&D) spend. The SHIELD II Phase 3 trial completion drove significant expenses. Here's a quick look at the R&D spend leading up to this point:

What this estimate hides is the specific allocation to CROs versus internal trial management, but the overall spend shows the investment required to generate the pivotal data. The market they are targeting is also substantial, with Surgical Site Infections (SSIs) representing a burden on healthcare systems costing hospitals tens of thousands of dollars per incident in a market over $10 billion.

When it comes to the actual U.S. commercialization launch, PolyPid Ltd. is in active discussions with multiple potential partners. As of May 2025, the company was advancing strategic partnership discussions and due diligence to maximize D-PLEX${ }{\text{100}}$'s market potential. Securing such a partner is seen as vital for obtaining essential capital and leveraging established sales infrastructure for market penetration, especially since the company's cash position as of September 30, 2025, was $18.8 million, expected to fund operations well into 2026.

Engagement with Key Opinion Leaders (KOLs) and surgeons is a necessary precursor to commercial success. PolyPid has already used input from surgeons, hospital administrators, and payers in their U.S. market access research to reinforce the value proposition of D-PLEX${ }{\text{100}}$. Furthermore, the company announced participation in a ROTH Capital Partners Virtual KOL Event scheduled for December 10, 2025, which is a direct step in building advocacy and education.

You can summarize the key external relationships and their status with this list:

• Strategic U.S. commercialization partner: Discussions ongoing as of May 2025.
• U.S. FDA: Pre-NDA feedback received December 3, 2025; NDA submission planned for early 2026.
• CROs: Costs reflected in R&D expenses of $17.6 million (9 months ended 9/30/2025).
• KOLs/Surgeons: Engaged via market research and scheduled event participation on December 10, 2025.
• IMOH: Fourth consecutive GMP inspection successfully completed September 16, 2025.

Finance: draft the cash flow impact analysis based on the $18.8 million cash balance as of September 30, 2025, by end of next week.

PolyPid Ltd. (PYPD) - Canvas Business Model: Key Activities

You're looking at the core actions PolyPid Ltd. is driving right now to bring D-PLEX₁₀₀ to market and build out its future. These aren't just ideas; they are concrete, measurable activities with hard numbers attached from the latest reporting periods.

Completing and submitting the D-PLEX₁₀₀ New Drug Application (NDA) to the FDA

The primary focus is locking down the regulatory submission for D-PLEX₁₀₀, the therapy for preventing abdominal colorectal surgical site infections (SSIs). PolyPid Ltd. received positive pre-New Drug Application (NDA) meeting minutes from the U.S. Food and Drug Administration (FDA) supporting the submission. The FDA agreed to a rolling NDA review, which means the company can start submitting completed sections in early 2026. The face-to-face pre-NDA meeting, initially scheduled for December 3, 2025, was canceled after the written feedback confirmed alignment. The Phase 3 SHIELD II trial demonstrated a 58% relative risk reduction in SSI incidence.

Advancing strategic discussions with potential commercial partners

PolyPid Ltd. is actively engaged in strategic partnership discussions with multiple potential U.S. partners, building on the momentum from the positive Phase 3 SHIELD II trial results announced in the second quarter of 2025. These discussions have progressed during the third quarter. The company is looking for partners with an established hospital sales infrastructure.

Manufacturing D-PLEX₁₀₀ under Good Manufacturing Practice (GMP)

A key activity here is ensuring commercial manufacturing readiness. PolyPid Ltd. successfully completed the Israeli Ministry of Health (IMOH) Good Manufacturing Practice (GMP) inspection. This marks the company's fourth consecutive successful GMP inspection of its manufacturing facility.

Ongoing research and development (R&D) for pipeline expansion (e.g., oncology, obesity)

While D-PLEX₁₀₀ is the near-term focus, R&D continues for pipeline expansion, which includes work in oncology, obesity, and diabetes. The financial commitment to this work is clear in the reported expenses:

The nine-month R&D expense of $17.6 million is an increase from $15.8 million for the same period in 2024.

Market access research and payer engagement for reimbursement strategy

To support the future commercial launch, PolyPid Ltd. completed a new U.S. market access study based on the SHIELD II results. This research provided validation of D-PLEX₁₀₀'s commercial potential, showing strong interest from both surgeons and hospital pharmacy directors. This value proposition research was presented at a major surgical congress. The company spent $1.4 million on Marketing and business development expenses for the nine months ended September 30, 2025.

The company's balance sheet as of September 30, 2025, held $18.8 million in cash and cash equivalents, which management expects will fund operations well into 2026. Finance: review the cash burn rate against the $25.7 million net loss for the nine-month period ending September 30, 2025.

PolyPid Ltd. (PYPD) - Canvas Business Model: Key Resources

You're looking at the core assets PolyPid Ltd. (PYPD) is banking on to move D-PLEX₁₀₀ toward commercialization. These aren't just ideas; they are tangible, validated components of their strategy as of late 2025.

Proprietary PLEX (Polymer-Lipid Encapsulation matriX) drug delivery technology

The PLEX platform is the engine here. It's a matrix built from alternating layers of polymers and lipids that trap the drug. This self-assembled structure creates a protected reservoir, which is key because it allows for controlled and continuous drug release over extended periods, specifically ranging from days to several months in a single application. For D-PLEX₁₀₀, this means the broad-spectrum antibiotic doxycycline is sustained at the surgical site for up to 30 days. This localized, prolonged delivery is designed to overcome systemic penetration issues common in some body locations and minimizes systemic side effects by keeping the drug concentrated where it's needed.

The PLEX technology supports several potential applications beyond infection prevention, including:

• Prevention of infections.
• Post surgical pain management.
• Inflammation control.
• Cancer tumor resection support.

Positive Phase 3 SHIELD II clinical data package for D-PLEX₁₀₀

The data package is robust, having successfully met its primary and all key secondary efficacy endpoints in the SHIELD II Phase 3 trial. The trial involved 798 patients with large abdominal surgery incisions (≥7 cm) for the primary endpoint assessment. Here's the quick math on the efficacy:

This positive readout keeps PolyPid Ltd. firmly on track for an NDA submission in early 2026.

FDA Breakthrough Therapy and Fast Track designations

The U.S. Food and Drug Administration (FDA) has recognized the potential of D-PLEX₁₀₀ to address a significant unmet need. The drug candidate holds several key designations:

• Breakthrough Therapy designation for the prevention of surgical site infections (SSIs) in patients undergoing elective colorectal surgery.
• Fast Track designation for the prevention of post-abdominal surgery incisional infections.
• Qualified Infectious Disease Product (QIDP) designations for two indications, including post-cardiac surgery sternal wound infection prevention.

Furthermore, the FDA agreed that the existing clinical data package, including the SHIELD II results, appears adequate to support NDA submission, and approved a rolling NDA review process, allowing PolyPid Ltd. to submit the first completed sections in early 2026.

Cash and equivalents of $18.8 million as of September 30, 2025

Financially, as of September 30, 2025, PolyPid Ltd. reported cash, cash equivalents, and short-term deposits totaling $18.8 million. This compares to $15.6 million on December 31, 2024. The company projects this balance is sufficient to fund operations well into 2026. Also, note that current maturities of long-term debt were reduced from $6.5 million as of June 30, 2025, down to $2.4 million as of September 30, 2025.

Experienced biopharma management and regulatory affairs team

The leadership team brings deep industry tenure, which is critical for navigating late-stage development and regulatory hurdles. The average tenure of the management team is cited at 3.4 years. Key experience includes:

• CEO Dikla Czaczkes Akselbrad has over 20 years of experience leading life sciences companies through transitions, including raising over $350 million in prior roles.
• Dalit Hazan, EVP R&D, Clinical, and Regulatory Affairs, brings over 25 years of expertise in the pharmaceutical industry, specializing in regulatory affairs and successful submissions to the FDA and EMA.
• Board member Yossi BenAmram is an experienced Senior Pharma Executive with over 34 years in the innovative and generic Pharma Industry, including over 22 years at Merck & Co. Inc.

Finance: draft 13-week cash view by Friday.

PolyPid Ltd. (PYPD) - Canvas Business Model: Value Propositions

You're looking at the core value PolyPid Ltd. (PYPD) offers to the surgical care ecosystem with its lead candidate, D-PLEX100. This isn't just another antibiotic; it's a delivery system designed to solve a persistent, costly problem: surgical site infections (SSIs).

The primary value is rooted in compelling clinical data from the Phase 3 SHIELD II trial in abdominal colorectal surgery. The product is engineered to provide local, controlled, and prolonged antibiotic activity directly at the surgical site, which is a significant departure from systemic dosing.

Here's the quick math on the efficacy demonstrated:

The mechanism itself is a key differentiator. PolyPid Ltd. (PYPD)'s proprietary PLEX (Polymer-Lipid Encapsulation matriX) technology allows for the precise delivery of Active Pharmaceutical Ingredients (APIs) over extended periods. This technology enables localized, controlled, continuous release of medication over durations ranging from several days to months. This contrasts with standard care, which lacks this sustained local protection.

The impact on the healthcare system is substantial, addressing both clinical outcomes and financial strain. The company completed U.S. market access research that reinforced the value proposition in reducing the significant clinical and economic burden of SSIs. By reducing SSIs, the product inherently supports improved patient outcomes and a reduction in the need for costly hospital readmissions or reinterventions, which were components of the primary endpoint.

The novel mechanism is designed to prevent SSIs, including those potentially caused by resistant bacteria, due to the high, localized concentration of the antibiotic delivered directly where it is needed most.

To give you a sense of the company's operational status supporting this value proposition as of late 2025:

• Research and development (R&D) expenses for the nine months ended September 30, 2025, totaled $17.6 million.
• The net loss for the three months ended September 30, 2025, was $7.5 million.
• Cash, cash equivalents, and short-term deposits as of September 30, 2025, stood at $18.8 million.
• The company expects this cash balance to fund operations well into 2026.

The FDA has provided supportive feedback on the existing clinical data package for D-PLEX100, agreeing it appears adequate to support an NDA submission, which is planned for early 2026.

PolyPid Ltd. (PYPD) - Canvas Business Model: Customer Relationships

You're looking at how PolyPid Ltd. (PYPD) builds and maintains connections with the key groups that drive its value-regulators, investors, and future commercial partners. This isn't about selling yet; it's about the high-stakes groundwork needed before a product hits the market.

Dedicated business development team managing high-stakes partnership negotiations

The focus here is securing the right commercial structure for D-PLEX₁₀₀ in the U.S. following the strong Phase 3 data. The relationship management is centered on detailed discussions with potential U.S. partners, leveraging the positive clinical profile to drive deal value. The company has an existing exclusive partner for Europe, named Advance, but the U.S. market remains a key negotiation front.

• Discussions with potential U.S. partners advanced in the quarter following Q2 2025 positive Phase 3 results.
• The company is actively seeking a U.S. commercialization partner as of late 2025.
• Marketing and business development expenses for the three months ended September 30, 2025, were $0.4 million.

Professional, consultative engagement with surgeons and hospital pharmacy directors

Engagement with the medical community is driven by the clinical evidence supporting D-PLEX₁₀₀. This consultative approach is vital for establishing the product's value proposition ahead of a potential U.S. launch. The data used to engage these stakeholders comes directly from the pivotal trial work.

• The Phase 3 SHIELD II trial enrolled a total of 800 patients.
• Topline results demonstrated a 58% reduction in Surgical Site Infections (SSIs) compared to the standard of care arm.
• The primary endpoint showed a statistically significant reduction of 38% ($p<0.005$).
• The U.S. Total Addressable Market (TAM) is estimated at just over 12 million total surgeries annually.
• The U.S. TAM includes approximately 4.4 million abdominal surgeries annually.

Regulatory collaboration with the FDA via rolling NDA submission

This is perhaps the most critical relationship right now-the one with the U.S. Food and Drug Administration (FDA). The success of this interaction directly impacts the timeline for commercialization. PolyPid Ltd. achieved a major de-risking event in December 2025.

The FDA provided supportive feedback on the pre-New Drug Application (NDA) meeting for D-PLEX₁₀₀ on December 3, 2025. This feedback confirmed the adequacy of the clinical data package, which includes results from the Phase 3 SHIELD II trial. The agency agreed to a rolling NDA review process, allowing PolyPid Ltd. to submit completed sections incrementally, with the first submissions anticipated in early 2026. The in-person meeting scheduled for December 3, 2025, was canceled as a result of the written response.

Investor relations and participation in financial conferences

Investor relations activities are geared toward maintaining financial support and providing transparency on the path to potential approval. The company actively engages with the financial community through presentations and one-on-one meetings. This is supported by the capital raised through warrant exercises, which extends the cash runway.

The company reported a cash position of $18.8 million as of September 30, 2025, which is expected to fund operations well into 2026. The firm secured $26.7 million in additional funding in June 2025 through warrant exercises.

Finance: draft 13-week cash view by Friday.

PolyPid Ltd. (PYPD) - Canvas Business Model: Channels

You're looking at how PolyPid Ltd. (PYPD) plans to get D-PLEX₁₀₀ to the surgeons and patients who need it, which is all about partnerships and regulatory milestones as of late 2025.

Future distribution network of a U.S. commercialization partner (in discussion)

PolyPid Ltd. (PYPD) is actively engaged in strategic partnership discussions for D-PLEX₁₀₀ in the United States. These discussions have progressed following the positive Phase 3 SHIELD II trial results announced in the second quarter of 2025. The Company is specifically advancing discussions with potential U.S. partners who possess an established hospital sales infrastructure. This focus on leveraging existing infrastructure is key to the planned distribution network upon potential approval. The discussions have progressed during the third quarter of 2025.

Direct sales force (post-partnership) targeting hospital systems and surgical centers

The current commercial strategy centers on securing a U.S. partner with the necessary sales infrastructure, which implies that a large, newly built direct sales force for the initial launch is not the primary channel. The Company's Chief Operating Officer, U.S., Ori Warshavsky, is involved in these partnership discussions. The focus is on partners whose existing infrastructure can target hospital systems and surgical centers effectively. What this estimate hides is the potential for a smaller, specialized PolyPid Ltd. (PYPD) team to support the partner post-launch.

Medical conferences and journals for clinical data dissemination

Dissemination of clinical data is being managed through investor and Key Opinion Leader (KOL) events, building on the strong Phase 3 data. PolyPid Ltd. (PYPD) presented at the Lytham Partners Fall 2025 Virtual Investor Conference on September 30, 2025. Furthermore, the Company planned to participate in a ROTH Capital Partners Virtual KOL Event on December 10, 2025, featuring a discussion on the clinical and economic burden of surgical site infections. These activities are funded through operating expenses, reflecting the push to commercial readiness.

Here's a quick look at the relevant spending through the third quarter of 2025:

The increase in these expenses is partly due to noncash charges related to performance-based stock units vesting after the successful SHIELD II trial.

Regulatory submissions (NDA/MAA) to the FDA and European authorities

Regulatory submissions are a critical channel to market access. PolyPid Ltd. (PYPD) remains on track to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in early 2026 for D-PLEX₁₀₀ to prevent abdominal colorectal surgical site infections. The FDA provided supportive feedback following the pre-NDA meeting, agreeing that the existing clinical data package appears adequate to support NDA submission and review. The agency approved a rolling NDA review process, allowing the first completed sections to be submitted in early 2026. The Company also anticipates submitting a Marketing Authorization Application (MAA) in Europe to follow the U.S. submission.

Key regulatory and manufacturing milestones supporting this channel include:

• NDA submission targeted for early 2026.
• Rolling NDA process approved by the FDA.
• Successful completion of the Israeli Ministry of Health (IMOH) Good Manufacturing Practice (GMP) inspection, marking the fourth consecutive successful inspection.
• Research and development expenses, net, for the nine months ended September 30, 2025, totaled $17.6 million, covering trial completion and regulatory preparation.

Finance: draft 13-week cash view by Friday.

PolyPid Ltd. (PYPD) - Canvas Business Model: Customer Segments

You're looking at the core groups PolyPid Ltd. (PYPD) targets with D-PLEX₁₀₀, their localized, 30-day doxycycline delivery platform for preventing surgical site infections (SSIs) following abdominal colorectal surgery. This is all about where the pain points-and the potential savings-are concentrated as of late 2025.

The primary focus is on the high-risk surgical environment, specifically colorectal procedures, which have shown concerning trends in infection rates.

• Hospital systems and surgical centers performing abdominal colorectal surgery
• Surgeons (colorectal, general) seeking improved SSI prevention tools
• Payers and health insurance companies focused on cost reduction from complications
• Patients undergoing high-risk surgical procedures for infection prevention

The financial and statistical rationale for targeting these groups is grounded in the high incidence and cost of SSIs in this specific surgical area. For instance, colorectal surgery infection rates reached as high as 7.4% in Q3 2024, an increase of 21% since Q4 2019.

Here's a quick look at the key numbers driving the value proposition for these segments:

Hospital systems and surgical centers performing abdominal colorectal surgery are motivated by reducing direct treatment costs and improving operational efficiency. They are the point of care where the product is administered during the procedure. The potential to avoid a complication costing $20,000 and adding nearly 10 days to a patient's stay is a major driver for adoption, especially given the high volume of these procedures.

Surgeons (colorectal, general) seeking improved SSI prevention tools are the key prescribers and champions. Their segment is directly influenced by clinical outcomes. The Phase 3 SHIELD II trial showed a statistically significant 58% relative risk reduction in SSIs. Furthermore, PolyPid Ltd. (PYPD) is actively advancing U.S. partnership discussions following these positive results, indicating a push toward commercial readiness for surgeon adoption.

Payers and health insurance companies focused on cost reduction from complications look at the macro-economic impact. With SSIs costing the U.S. system over $10 billion annually, a product that demonstrably lowers the rate of these costly events is attractive for formulary inclusion or coverage decisions. PolyPid Ltd. (PYPD) conducted U.S. market access research that reinforced this value proposition for hospital administrators and payers.

Patients undergoing high-risk surgical procedures for infection prevention are the ultimate beneficiaries, though they are often reached indirectly through provider choice. For patients, avoiding an SSI means avoiding increased morbidity, potential death (approximately 11,000 SSI-related deaths annually in the U.S.), and a longer recovery. D-PLEX₁₀₀ is designed to provide local, prolonged antibiotic protection for up to 30 days post-surgery.

PolyPid Ltd. (PYPD) itself is in a critical pre-launch phase, with a New Drug Application (NDA) submission for D-PLEX₁₀₀ expected in early 2026. As of September 30, 2025, the company held $18.8 million in cash and equivalents, expecting this to fund operations well into 2026.

Finance: draft 13-week cash view by Friday.

PolyPid Ltd. (PYPD) - Canvas Business Model: Cost Structure

You're looking at the core outflows for PolyPid Ltd. (PYPD) as they push D-PLEX ${ }{\text{100}}$ toward commercialization. Honestly, in late 2025, the cost structure is heavily weighted toward getting that New Drug Application (NDA) across the finish line and preparing for market entry. It's all about clinical transition costs right now.

The most significant financial commitment in the operating structure relates to the science itself. For the nine months ended September 30, 2025, Research and Development (R&D) expenses, net, totaled $17.6 million. This was up from $15.8 million for the same nine-month period in 2024, driven by the final push on the SHIELD II Phase 3 trial completion and the intensive work preparing for regulatory submissions. That's where the bulk of the burn is going.

General and administrative (G&A) expenses also saw an increase, hitting $5.4 million for the nine months ended September 30, 2025, up from $3.3 million the prior year. To be fair, a good chunk of that increase in both G&A and marketing/business development was tied to noncash expenses from performance-based stock options vesting after the successful SHIELD II trial readout.

Here's a quick look at the key operating expenses for the nine months ended September 30, 2025, compared to the prior year period:

The regulatory and quality assurance costs are embedded within the R&D and G&A lines, reflecting the critical path activities PolyPid Ltd. is undertaking. You know the goal: the NDA submission is targeted for early 2026, which means significant spending on Chemistry, Manufacturing, and Controls (CMC) modules and ensuring full Good Manufacturing Practice (GMP) compliance for commercial supply.

Beyond the immediate regulatory hurdles, the cost structure includes forward-looking investments:

• Costs associated with advancing U.S. commercial partnership discussions.
• Manufacturing scale-up and supply chain development for D-PLEX ${ }{\text{100}}$.
• Finalizing key regulatory components for the NDA submission.

The company is actively managing its cash position, which stood at $18.8 million as of September 30, 2025, and they expect this balance to fund operations well into 2026. Also, they successfully secured $26.7 million in additional funding in June 2025 through warrant exercises, which was designed to extend the runway beyond the anticipated FDA approval timeline. Finance: draft 13-week cash view by Friday.

PolyPid Ltd. (PYPD) - Canvas Business Model: Revenue Streams

You're looking at the revenue picture for PolyPid Ltd. (PYPD) as of late 2025, and honestly, it's all about future potential right now, which is typical for a late-stage biopharma firm. The current reality is that PolyPid Ltd. is still pre-commercial, meaning there are no product sales rolling in yet.

For the nine months ended September 30, 2025, the company reported a net loss of $25.7 million. This figure reflects the ongoing investment in R&D, particularly related to the SHIELD II Phase 3 trial completion, and general administrative costs, not revenue from product sales.

The primary, near-term revenue driver is expected to come from D-PLEX100 sales once it hits the market. Following positive feedback from the U.S. Food and Drug Administration (FDA) on the pre-New Drug Application (NDA) meeting minutes in December 2025, the NDA submission is on track for early 2026. Given the expedited designations, FDA approval for D-PLEX100 could potentially arrive by late 2027. Post-approval, revenue will flow from direct sales to hospitals and, more immediately, from partnership structures.

A key component of the model involves securing a U.S. commercialization partnership. While the specific terms for a U.S. deal aren't set, we can look at the existing European agreement with ADVANZ PHARMA Corp. as a strong template for potential upfront payments and milestones. This structure is what PolyPid Ltd. is actively trying to replicate for the U.S. market.

Also, PolyPid Ltd. is building out future revenue potential by leveraging its proprietary PLEX technology platform beyond the lead indication. This is about creating value from the core technology itself, not just D-PLEX100.

• Platform Licensing in Oncology: PolyPid Ltd. has a research and development collaboration with ImmunoGenesis, Inc., focusing on utilizing the PLEX Technology to enhance cancer immunotherapy with a STING agonist drug candidate.
• Future Licensing Fees: The company will explore additional opportunities to bring value through innovative collaborations, which would generate licensing fees or milestone payments for applying the PLEX platform to other drug candidates or indications.

The company's cash balance as of September 30, 2025, was $18.8 million, which management expects will fund operations well into 2026, making those partnership discussions defintely critical.