PharmaShots Interview: PolyPid’s Dikla Czaczkes Akselbrad Shares Insights on the P-III (SHIELD I) Trial of D-PLEX100

In an interview with PharmaShots, Dikla Czaczkes Akselbrad, Executive Vice President, Chief Financial Officer at PolyPid shares her views on Q3’21 financial results & P-III (SHIELD I) trial of D-PLEX100 in patients with incisional SSIs in post-abdominal surgery

Shots:

The P-III (SHIELD I) trial evaluates the efficacy and safety of D-PLEX100 in ~500 patients with incisional SSIs in post-abdominal surgery. The trial continues to enroll ~900 patients in Q2’22 at 60 centers across the US, EU & Israel
The 1EPs of the trial is the combination of incisional SSIs and mortality rate as measured by the proportion of patients with SSI events as determined by a blinded and independent adjudication committee or mortality within 30 days post-surgery
In the P-II trial, D-PLEX100 showed good efficacy and safety profile when administered concurrently with the SoC in the prevention of SSI in patients undergoing abdominal surgery that leads reduction in infections

Tuba: What do you mean by Cash Runway and how it will impact the company’s product development and pipeline?

Dikla Czaczkes Akselbrad: PolyPid ended the third quarter of 2021 with $42.0 million. This strongly indicates that even without cash coming in from any future commercialization deals, we have sufficient cash on hand to complete 2022 while running a single pivotal Phase 3 trial which is sufficient, provided the study results are adequate, for potential approval of a D-PLEX₁₀₀ New Drug Application.

We also look forward to making progress in our oncology program. We are currently in the preclinical stages to test the efficacy and safety of OncoPLEX in reducing local tumor reoccurrence and the potential spread of cancer cells, beginning with Glioblastoma Multiforme (GBM).

Tuba: Give us insights into your Phase 3 SHIELD I and II trial design?

Dikla Czaczkes Akselbrad: SHIELD I (Surgical site Hospital-acquired Infection prEvention with Local D-PLEX) is a prospective, multinational, multicenter, randomized, double-blind Phase 3 trial designed to assess the efficacy and safety of D-PLEX₁₀₀ for the prevention of incisional surgical site infections (SSIs) in post-abdominal surgery. The primary endpoint of the trial is the combination of incisional SSIs and mortality rate as measured by the proportion of subjects with either an SSI event, as determined by a blinded and independent adjudication committee, or mortality for any reason within 30 days post-surgery.

Phase 3 SHIELD I has over 500 patients enrolled. The trial will continue with patient enrollment toward approximately 900 patients until the second quarter of 2022, in about 60 centers across the United States, Europe, and Israel.

Provided the study results are adequate, the U.S. Food and Drug Administration (FDA) has previously agreed that a single pivotal Phase 3 study is sufficient for the potential approval of D-PLEX₁₀₀ for the prevention of SSIs in colorectal surgery.

Tuba: Explain about D-PLEX100 and its MoA, RoA, formulation, and other details?

Dikla Czaczkes Akselbrad: D-PLEX₁₀₀ is a novel product pairing PLEX (Polymer-Lipid Encapsulation MatriX) technology with doxycycline, a broad-spectrum antibiotic, which provides local high concentration directly at the surgical site over a period of four weeks to effectively prevent the risk of SSIs through its cutting-edge extended-release mechanism. The product is supplied as a fine, granulated powder that is hydrated and turned into a paste immediately before being applied locally by the surgeon at the incision surgical site.

D-PLEX₁₀₀ needs minimal application training and fully biodegrades over time. D-PLEX₁₀₀ demonstrated in Phase 2 clinical trial an excellent efficacy and safety profile when administered concomitantly with the Standard of Care (SoC) in the prevention of SSI (superficial and deep) in patients undergoing abdominal surgery, leading to a statistically significant reduction in infections compared to SoC alone.

Tuba: Throw some light on the epidemiology of surgical site infections.

Dikla Czaczkes Akselbrad: There is a global unmet need of addressing the estimated $10 billion annual cost of SSIs to the healthcare system. As the second most prevalent type of Healthcare Acquired Infection (HAI), SSIs are responsible for 20 percent of all HAIs in US hospitals and often result in extended hospital stays and readmission, placing a significant financial burden on the healthcare systems while risking patients’ lives. The rates of SSI are higher in abdominal surgery, particularly in colorectal surgery with studies showing rates of up to 30 percent in high-risk patients. PolyPid’s simple solution has the potential to save healthcare systems time and money, while also saving patient lives by implementing the latest drug administration innovations.

Tuba: What is your commercialization strategy after US FDA approval?

Dikla Czaczkes Akselbrad: After FDA approval, we have two commercialization strategies - one for the U.S. and one for the rest of the world. In the US, we are building our own internal capabilities while advancing discussions with large pharmaceuticals and med-device companies for selective partnership. We strongly believe that to maximize the value of D-PLEX₁₀₀ as well as the value of our pipeline, we should have our own internal capabilities and relationship with our customers, rather than using a partner. Outside of the US, we are aiming to sign licensing deals with pharmaceutical companies that have experience selling within the surgical suite.

Tuba: Tell us about the OncoPLEX development platform, the technology behind and its applications.

Dikla Czaczkes Akselbrad: OncoPLEX utilizes PolyPid’s novel PLEX technology to provide controlled local exposure to docetaxel, one of the most widely used chemotherapy agents, for a few weeks postoperatively to the tumor resection cavity. This will potentially reduce the exceedingly high local tumor recurrence in certain tumors, tumor spread, and ultimately prolong patient survival. Its novelty allows for up to three weeks of local chemotherapy with minimal or no systemic exposure.

In September 2021, PolyPid announced positive results in two animal models of the devastatingly aggressive brain cancer, GBM, which demonstrated that a single local treatment of OncoPLEX significantly inhibited tumor growth and prolonged survival. We have conducted a successful pre-IND meeting with the FDA on clinical and pre-clinical development plans for GBM indication.

Tuba: Which other drugs are being developed in your pipeline under the PLEX platform?

Dikla Czaczkes Akselbrad: Our current focus is on pairing PLEX with chemotherapy. We are constantly evaluating our future program to identify new areas where we can add value on our own or with other biotech companies pairing novel antibodies. We have shown in the past that the PLEX platform works well with small molecules as well as large molecules, peptides, and sRNA. The PLEX platform is ideal when local administration is preferred to systemic administration to avoid toxicity while addressing localized disease and the associated difficulties of achieving sustainable therapeutic drug levels at the site. This therapeutic strategy can work well for companies interested in the life-cycle management of already approved molecules and for new innovative ones where effective local disease eradication is the major clinical goal.

Tuba: How does PolyPid plan to target cash runway in the coming few months?

Dikla Czaczkes Akselbrad: Our cash position is strong, with key milestones identified for 2022. We are also evaluating future financial opportunities. We have also filed an ATM program that will allow us to issue shares when the time is right.

Source: Hospital + Healthcare

About Author:

Dikla Czaczkes Akselbrad is an Executive Vice President and Chief Financial Officer at Polypid. She holds an MBA in finance and a BA in accounting and economics both from Tel Aviv University and is a certified public accountant in Israel