About PolyPid

Polypid Ltd., a clinical-stage biopharmaceutical company, focuses on developing targeted, locally administered and prolonged-release therapeutics using its proprietary PLEX technology. The company's product candidates are designed to address diseases with high unmet medical needs by pairing its PLEX technology with drugs already approved by the U.S. Food and Drug Administration (FDA) or innovative drug candidates to achieve a novel therapeutic effect. The company's PLEX technology is designed to deliver drugs directly to targeted treated sites in the body at predetermined release rates and predetermined durations ranging from several days to several months. The company's PLEX technology and product candidates have the potential to significantly improve the management of a variety of medical conditions, including surgical site infections (SSIs) and cancer. The company's lead product candidate, D-PLEX100, is in a pivotal Phase 3 confirmatory trial for the potential approval for prevention of open abdominal SSIs. D-PLEX100 pairs the company's novel proprietary PLEX technology with doxycycline, a first-line, broad spectrum and FDA-approved antibiotic D-PLEX100 is administered directly into the surgical site during surgery, and provides a prolonged and continuous release of the broad-spectrum antibiotic doxycycline, resulting in high local concentration of the drug for a period of 30 days for the prevention of SSIs, including SSIs caused by standard of care antibiotic-resistant bacteria. D-PLEX100, if approved, would be a significant improvement over the standard of care, which includes systemic administration of antibiotics. The company initiated two Phase 3 trials of D-PLEX100, which it refers to as SHIELD I and SHIELD II, for the prevention of abdominal (soft tissue) SSIs in the third and fourth quarters of 2020, respectively. In May 2021, the FDA agreed in a Type B meeting that a single pivotal Phase 3 study is sufficient, provided the study results are adequate, for potential approval of a D-PLEX100 new drug application (NDA) for the prevention of SSIs in colorectal surgery. In September 2022, the company announced top-line results from the SHIELD I Phase 3 study of D-PLEX100 for the prevention of SSIs in abdominal surgery. The SHIELD I study demonstrated a good safety profile of D-PLEX100 with no increase in serious or severe treatment emergent adverse events compared to standard of care. In November 2022, the company provided the FDA with available data from the SHIELD I study as part of a Type D meeting request. Following positive type D meeting communication with the FDA, which took place in January 2023 on the SHIELD I Phase 3 data, the company has a clear regulatory pathway towards a potential NDA submission. The FDA stated that the ongoing SHIELD II study, which as of December 31, 2022, had enrolled over 200 patients, including approximately 40 patients with the appropriate large open surgical incisions, could potentially serve as such a study. The FDA also recognized that D-PLEX100's proposed indication is for the prevention of infection and has the potential for wide use. 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, 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. SHIELD II patient recruitment is expected to resume in the second quarter of 2023 with the enrollment of an estimated 550 additional patients. Total recruitment time into the study is anticipated to be approximately 12 months and top-line results are expected in mid-2024. Unblinded interim analysis is planned to be conducted once approximately 400 patients complete their 30-day follow-up. In October 2019, the company reported topline data from its Phase 2 clinical trial of D-PLEX100 for the prevention of SSIs in patients undergoing abdominal (soft tissue) surgery. In December 2019, the company initiated a potentially pivotal Phase 3 clinical trial of D-PLEX100 for the prevention of post-cardiac sternal (bone) SSIs, and it enrolled the first patient in February 2020. The company paused enrollment in this trial as it determined to initially focus on abdominal (soft tissue) surgeries. In February 2020, the company held an end of Phase 2 meeting with the FDA and in May 2021, the company held a Type B meeting with the FDA to discuss its D-PLEX100 development plans following which the FDA agreed that a single pivotal Phase 3 study is sufficient, provided the study results are adequate, for potential approval of a D-PLEX100 NDA for the prevention of SSIs in colorectal surgery. Following this agreement, the company determined to focus on its SHIELD I clinical trial. The company intends to pursue a broad label for D-PLEX100 for the prevention of SSIs, the scope of which will depend on the clinical data generated from its Phase 3 clinical trials and discussions with the FDA and the European Medicines Agency (EMA). The company intends to seek approval of D-PLEX100 under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act, or FFDCA, which provides an abbreviated pathway for marketing approval by the FDA in the United States, and will seek approval under the comparable hybrid application pathway in the European Union. In November 2020, the company received breakthrough therapy designation from the FDA for the prevention of SSIs in patients undergoing elective colorectal surgery based on the clinical results of its Phase 2 trial. In September 2022, the company received confirmation from the EMA that D-PLEX100 is eligible for submission of a Marketing Authorization Application (MAA) in the European Union (EU) under the EMA's centralized procedure. The centralized process eligibility is granted to D-PLEX100 under the Therapeutic Innovation criteria which underscores that D-PLEX100 potentially provides a new alternative to patients in preventing post abdominal SSIs. As it has done with the FDA in the United States, the company is preparing for expected near-term interactions with the European regulatory authorities regarding D-PLEX100, which are anticipated in the first half of 2023. In addition to its lead program D-PLEX100, the company's pipeline includes an early-stage oncology program, OncoPLEX, PolyPid's lead intra-tumoral cancer therapy drug candidate. OncoPLEX utilizes the company's PLEX technology to provide controlled local exposure to docetaxel, one of the most widely used chemotherapy agents, directly at the tumor site for several weeks to potentially reduce local tumor reoccurrence, the potential spreading of cancer cells, and ultimately improve the overall survival rate of cancer patients. The OncoPLEX intra-tumoral cancer therapy program has been evaluated successfully in various animal tumor models, including colon carcinoma and glioblastoma. The company is finalizing chemical, manufacturing and control (CMC) processes for OncoPLEX as it continues its efforts to begin clinical development. The company intends to expand research collaborations with biopharmaceutical companies leveraging its PLEX Technology. SHIELD I pharmacokinetic data validated the PLEX technology platform in a large clinical trial, providing local and controlled release of drug molecules directly at the disease target organ over a pre-determined period of time. PLEX can be paired with a wide variety of marketed drugs or product candidates, including small molecules, peptides, antibodies and nucleic acid-based drugs. Pairing biopharmaceutical companies approved drugs or product candidates with PLEX has the potential to overcome limitations in terms of efficacy or safety due to their systemic delivery and potentially extend the drug's clinical benefit and lifecycle before and after patent expiration. The company intends to further engage in discussions with leading biopharmaceutical companies regarding licensing its PLEX technology for potential application in various therapeutic areas, including oncology. The company continues to invest in its state-of-the-art, sterile manufacturing facility that is current good manufacturing practices (cGMP) certified by the IMOH and inspected by an EU-qualified person enabling cGMP manufacturing of D-PLEX100 for its SHIELD II trial. The company has recently successfully completed the expansion of its manufacturing capabilities and is in final stage of commercial process validation. The company intends to use this manufacturing capacity as the basis to build a fully integrated biopharmaceutical company, supported by its in-house research and development and regulatory team and its anticipated commercial infrastructure. Pipeline The company's PLEX technology consists of a proprietary matrix of several thousand layers of chemically inactive and biocompatible polymers and lipids that physically embed the drug within the layers. A drug stored within the PLEX layers is released over time in a controlled manner and in customizable, predetermined amounts at the local site where it is administered. PLEX technology is designed to protect the embedded medication from the natural enzymes and other biochemicals in the body that would otherwise degrade or alter the drug. Over time, natural hydration in the body disintegrates the layers of PLEX, from the outer layer to the inner layers, which triggers a release of the medicine in an unmodified, active form. These characteristics may enable the company's PLEX product candidates to be efficacious using only a small fraction of the medicines required in systemic administration. The company's PLEX platform technology may have broad therapeutic application for other localized medical conditions. Because the company's PLEX technology is designed to be agnostic to the nature and size of the underlying drug, it has the potential to be paired with a wide variety of marketed drugs or product candidates in development, including small molecules, peptides, antibodies and other proteins, as well as nucleic acid-based APIs, to create novel therapies in a broad range of locally delivered applications. The company is pursuing research and development programs for its PLEX platform in a variety of other potential indications where it has identified a targeted active pharmaceutical ingredient, or API, for use with its PLEX technology, including for the treatment of cancer, inflammation and pain. The company will consider licensing rights to its PLEX technology for use with various biologics and small molecules. As of March 26, 2023, the company had 146 issued patents, including utility and composition of matter patents. Additionally, it has five patent applications that have been allowed in Canada, New-Zealand and in the Philippines, and 10 pending patent applications in the United States, China, Europe, India, Singapore, South Korea and Thailand, and one published Patent Cooperation Treaty (PCT) application. The company's issued patents expire between 2029 and 2035. Strategy The key elements of the company's strategy are to successfully complete clinical development of D-PLEX100 for the prevention of SSIs; pursue expedited regulatory pathways for its product candidates; execute on its go-to-market commercial strategy; expand its product pipeline for additional indications using its PLEX technology; pursue research collaborations with biopharmaceutical companies; and build a fully integrated biopharmaceutical company utilizing its manufacturing facility. Marketing, Sales and Distribution Given the company's stage of development, it has limited internal marketing, sales and distribution capabilities. The company has established a wholly-owned United States subsidiary, PolyPid Inc., a Delaware corporation with operations in New Jersey, to support its potential commercialization efforts in the United States and its clinical development program. The company intends to launch D-PLEX100 and any future product candidates in the United States following the FDA approval using its commercial capabilities. The company is also exploring potential partnering opportunities with leading pharmaceutical companies focusing on hospital business to maximize its commercial success and launch of any approved products in the United States. The potential clinical and economic benefits of D-PLEX100 will support its commercial launch under existing Medicare rates given the associated mortality, morbidity and cost burden of SSIs and the associated penalties imposed on hospital reimbursement from CMS. Outside the United States, the company intends, where appropriate, to pursue commercialization relationships, including strategic alliances and licensing, with pharmaceutical companies and other strategic partners that are equipped to market and sell its products through their well-developed sales, marketing and distribution organizations in such countries. On August 2, 2022, the company entered into a license, distribution and supply agreement with Mercury Pharma Group Limited, under the trade name Advanz Pharma Holdings, or Advanz, pursuant to which the company granted the exclusive right to Advanz to market, advertise, promote, distribute, offer for sale, sell and import its product D-PLEX100 for the prevention of post abdominal surgery incisional infection and/or post cardiac surgery sternal infection in the European Economic Area and the United Kingdom. The term of the license is until the later of December 31, 2035, or 10 years after the first commercial sale of D-PLEX100. The license is also terminable by either party under certain limited circumstances. In addition, the company will supply D-PLEX100 to Advanz for a transfer price and will be entitled to royalties on net sales in double-digit percentages of up to mid-twenties. Intellectual Property The company's patent estate includes patents and patent applications with claims directed to its PLEX technology platform, D-PLEX100 product candidate and claims for potential future product candidates. As of March 26, 2023, the company's patent estate included 146 issued patents, including utility and composition of matter patents, five allowed patent applications, 10 pending patent applications and one published PCT application for its product candidates and methods of treatment. The company's patents and patent applications primarily relate to a polymer-lipid-based platform for sustained release of an active pharmaceutical agent at a target site. It has 35 issued patents, and one pending patent application in various countries worldwide related to compositions for sustained release of an API, including a lipid-saturated matrix formed from a biodegradable polymer, as well as methods for producing such compositions and methods of treatment through the use of such compositions. The company also has 17 issued patents and one pending patent application in various countries worldwide related to compositions for sustained release of an API, including a lipid-saturated matrix formed from a non-biodegradable polymer, as well as methods for producing such compositions and methods of treatment through the use of such compositions. It also has 12 issued patents in various countries worldwide related to compositions for sustained release of a nucleic agent, including a lipid-saturated matrix formed from a biodegradable polymer, as well as methods for producing such compositions and methods of treatment through the use of such compositions. The company also has an issued Australian patent related to compositions for sustained release of peptidic molecules, as well as methods for producing such compositions and methods of treatment through the use of such compositions. It also has 25 issued patents and two pending patent applications in various countries worldwide related to methods for treating bone fractures through the use of biocompatible fillers coated with sustained release antibiotic compositions, along with 15 issued patents and two allowed patent applications in various countries worldwide related to methods for treating peri-implantitis and 41 issued patents, three allowed and six pending patent applications in various countries worldwide related to methods for preventing and treating SSIs through similar processes. The company also has one published PCT application related to compositions and methods for the treatment of solid tumors. The company's patent estate includes 11 issued United States patents, as well as issued patents and/or pending patent applications in Australia, Brazil, Canada, China, the Eurasian Patent Organization, the European Patent Office, Hong-Kong, India, Israel, Japan, Mexico, New Zealand, the Philippines, Singapore, South Africa, South Korea, Thailand and the United States. Its issued patents are expected to remain in effect between 2029 and 2035. In addition to patents, the company has seven registered trademarks. 'BonyPid' which is registered in the European Union Intellectual Property Office and in Israel, 'PolyPid' which is registered in the United States, Israel, China and in the following European Union countries: Benelux, France, Germany, Spain, Austria, Italy, the United Kingdom, Ireland and Portugal, 'Bacfenssi' which is registered in the United States, the European Union Intellectual Property Office, Great Britain, China, Israel and Russia and pending in the Switzerland, Iceland, Liechtenstein and Norway, 'Opzifend' which is registered in the United States, the European Union Intellectual Property Office, Great Britain, China, Israel and Russia and pending in Switzerland, Iceland, Liechtenstein and Norway, and 'Ssisurg', 'Elyfssi' and 'Bacyssio' which are registered in Israel. Government Regulation Prior to commencing the first clinical trial with a product candidate, the company must submit the results of the preclinical tests and preclinical literature, together with manufacturing information, analytical data and any available clinical data or literature, among other things, to the FDA as part of an IND. The company's business activities, including but not limited to, research, sales, promotion, distribution, medical education and other activities are subject to regulation by numerous regulatory and law enforcement authorities in the United States in addition to the FDA, including the Department of Justice, the Department of Health and Human Services (HHS) and its various divisions, including CMS and the Health Resources and Services Administration, the Department of Veterans Affairs, the Department of Defense and state and local governments. The company's operations use chemicals and produce waste materials and sewage and require permits from various governmental authorities including, local municipal authorities, the Ministry of Environmental Protection and the Ministry of Health. The Ministry of Environmental Protection and the Israeli Ministry of Health (MOH), local authorities and the municipal water and sewage company conduct periodic inspections in order to review and ensure the company's compliance with the various regulations. History PolyPid Ltd. was founded in 2008. The company was incorporated under the laws of Israel in 2008.