PDS Biotechnology(US:PDSB)2023-03-28 21:02Immunotherapy Development - The company is developing a pipeline of targeted cancer and infectious disease immunotherapies based on proprietary platforms Versamune® and Infectimune™, aiming to induce large quantities of high-quality CD4 and CD8 T cells[17]. - The company aims to address a wide range of cancers, including HPV-positive cancers and various solid tumors[17]. - The company is focused on overcoming challenges in immunotherapy, such as generating adequate quantities of high-quality T cells and minimizing systemic toxicities[23]. - The combination of Versamune and IL-12 is patented by the company, streamlining the registrational process for its therapies[21]. - Versamune has shown the ability to reduce the Treg to CD8 T cell ratio, enhancing tumor susceptibility to immune destruction[39]. - In preclinical studies, Versamune-based therapy resulted in complete tumor regression after a single subcutaneous injection[52]. - PDS0101 demonstrated immunological activity at all three doses studied, leading to clinical regression of cervical lesions in patients[52]. - PDS0301, when combined with Versamune, has shown potential for significant disease control by shrinking tumors and prolonging patient survival[58]. - PDS0102 is designed to treat TARP-associated cancers, showing safety and immunogenicity in preclinical studies[87]. - PDS Biotech is developing a universal influenza vaccine using the Infectimune platform, aiming for broad protection against multiple strains[63]. - PDS0201 is in preclinical development targeting tuberculosis, a leading cause of death from a single infectious agent, with 1.5 million deaths reported in 2020[66]. Clinical Trials and Results - In a Phase 2 clinical trial, the combination of PDS0101 and PDS0301 resulted in a median overall survival of 21 months for ICI refractory head and neck cancer patients, compared to a historical median survival of 3-4 months with checkpoint inhibitors[21]. - The VERSATILE-002 Phase 2 clinical trial is actively recruiting patients to evaluate the combination of PDS0101 and KEYTRUDA® for recurrent/metastatic head and neck cancer[71]. - Preliminary efficacy data from the VERSATILE-002 trial showed an objective response rate of at least 23.5% in the ICI refractory group[79]. - In the NCI-led Phase 2 trial, 41.2% of patients achieved tumor shrinkage greater than 30% with the triple combination therapy[78]. - The median overall survival for ICI refractory patients receiving the triple combination therapy was reported at 21 months, compared to historical data of 3-4 months[82]. - In ICI naïve patients, the objective response rate with the triple combination was 88%, significantly higher than the less than 25% reported with FDA-approved ICIs[82]. - The ongoing Phase 2 trial with MD Anderson Cancer Center is investigating the combination of PDS0101 with standard-of-care chemoradiotherapy for locally advanced cervical cancer[84]. - PDS0101 treatment resulted in 100% objective response rate and 89% complete response rate in patients treated with combination therapy[88]. - 1-year disease-free survival and overall survival rates were both 89% in patients receiving PDS0101 combined with CRT[88]. - Safety data from the trials indicate that 48% of patients experienced Grade 3 treatment-related adverse events, with no Grade 5 events reported[82]. Regulatory and Financial Aspects - The FDA granted Fast Track designation to PDS0101 in combination with KEYTRUDA® to expedite its development for serious conditions[18]. - The next step for PDS0101 is transitioning into Phase 3 clinical development, with an amended IND filing planned for Q3 2023[108]. - The company plans to progress PDS0102 and PDS0103 to IND submissions in 2023 for first-in-human trials[109]. - The company has not generated any product revenue to date and has incurred net losses each year since inception[100]. - The biotechnology and pharmaceutical industries are characterized by intense competition, with established companies and development-stage biotechnology companies competing in immunotherapies and vaccines[134]. - PDS anticipates facing increasing competition as new immunotherapies enter the market, which may affect its ability to compete based on efficacy, safety, and pricing[136]. - The FDA approval process for biological drug products requires substantial time and financial resources, with various regulatory steps that must be completed before marketing[138]. - The FDA may impose a clinical hold or partial clinical hold on clinical trials, which delays or suspends investigations, with a written explanation provided within 30 days[143]. - The company is seeking nondilutive financing to support the next stage of clinical development for its product candidates[97]. Intellectual Property and Agreements - As of December 31, 2022, the company holds seven (7) U.S. patents and nineteen (19) pending U.S. patent applications related to its Versamune platform, with issued patents expiring between 2026 and 2033[111]. - The company has an exclusive worldwide license from Merck & Cie for (R)-DOTAP and its related pharmaceutical compositions, which are significant for its immunotherapy products[112]. - The company has licensed patented antigens from the U.S. government for use in cationic lipid immunotherapies, including TARP peptide-based therapies for prostate and breast cancers[113]. - A non-exclusive agreement was entered into with the University of Georgia Research Foundation to develop COBRA universal influenza antigens for a clinical trial of a universal influenza vaccine[114]. - On December 30, 2022, the company entered into a License Agreement with Merck KGaA, which includes a one-time cash payment of $5.0 million and the issuance of 378,787 shares valued at $5.0 million[116]. - The company agreed to make milestone payments totaling up to $11 million upon achieving certain development milestones and up to $105 million based on aggregate sales levels of the product under the Merck KGaA License Agreement[117]. - A royalty of 10% on aggregate net sales of the product is to be paid to Merck KGaA, applicable for ten years after the first commercial sale or until the expiration of the licensed patents[118]. - The company has a Patent License Agreement with NIH, which includes a nonrefundable minimum annual royalty of $5,000 and earned royalties of 2% on net sales[122]. - Under the NCI Patent License Agreement, the company obtained a nonexclusive, worldwide license to develop TARP peptide-based therapies, with royalties and benchmark payments required[123]. - The Cooperative Research and Development Agreement with NCI includes a commitment of up to $1,000,000 for the first year and a minimum of $750,000 per year for subsequent years to support clinical research activities[126]. Market and Compliance Challenges - Coverage and reimbursement for PDS's product candidates depend on third-party payors, with significant uncertainty regarding approval and pricing processes[211]. - The Medicaid Drug Rebate Program requires pharmaceutical manufacturers to enter into national rebate agreements to receive federal matching funds[204]. - PDS may face civil, criminal, and administrative penalties if found in violation of healthcare laws, which could adversely affect its operations and financial results[207]. - The marketability of PDS's products may suffer if adequate coverage and reimbursement are not provided by government and third-party payors[213]. - Increased scrutiny of pharmaceutical companies by federal and state enforcement bodies may lead to investigations and compliance challenges for PDS[208]. - PDS expects ongoing pricing pressures due to managed healthcare trends and legislative changes impacting reimbursement rates[214]. - Future state and federal privacy legislation may arise, potentially impacting PDS's operations and compliance costs[210]. - Recent healthcare reforms in the U.S. may delay marketing approval for product candidates and affect sales capabilities[216]. - The Patient Protection and Affordable Care Act (PPACA) has significantly impacted healthcare financing and delivery[216].