PDS Biotechnology(US:PDSB)2024-03-28 21:16Cancer Immunotherapy Development - The company is developing a pipeline of targeted cancer immunotherapies, including Versamune® and PDS01ADC, aimed at enhancing T cell responses in the tumor microenvironment [18]. - In a Phase 2 trial, the combination of PDS0101 and PDS01ADC resulted in a median overall survival of approximately 20 months for ICI-resistant patients, compared to historical median survival of 3-4 months [21]. - The company presented data at the 2023 ASCO conference showing safety and efficacy in an immune checkpoint inhibitor naïve cohort for HPV16-positive head and neck cancer [23]. - Interim data from the VERSATILE-002 Phase 2 trial indicated promising immune response results when combining PDS0101 with Merck's Keytruda® [26]. - The company announced a successful Type B meeting with the FDA regarding a registrational trial for the triple combination therapy for recurrent/metastatic HPV-positive head and neck cancer [22]. - In October 2023, data showed that PDS0101 in combination with SOC chemoradiotherapy led to a rapid decline in ctHPV-DNA, a potential predictive biomarker of treatment response [25]. - The proprietary combination of Versamune® and PDS01ADC is designed to overcome tumor immune suppression, which is patented by the company [21]. - Versamune® has shown the potential to promote efficient activation and robust expansion of polyfunctional CD8 killer T cells and CD4 helper T cells in lymph nodes [47]. - In preclinical studies, Versamune® demonstrated a reduction in the Treg/CD8 T cell ratio, enhancing tumor susceptibility to destruction by killer T cells [49]. - PDS0101, a Versamune® based immunotherapy, induced complete regression of tumors after a single subcutaneous injection in preclinical studies [62]. - In a Phase 1 clinical trial, PDS0101 was immunologically active at all doses studied, leading to clinical regression of cervical lesions in patients [62]. - In a Phase 2 clinical trial, 75% of ICI naïve patients treated with PDS0101 and PDS01ADC were still alive at 36 months, with median overall survival not yet reached [68]. - The combination therapy of PDS0101 and PDS01ADC showed an objective response rate (OR) of 88% in ICI naïve patients, with 4 out of 7 patients' responses ongoing at a median of 17 months [81]. - In ICI resistant patients, 63% (5 out of 8) achieved an OR with PDS01ADC at 16.8 mcg/kg compared to 7% (1 out of 14) at 8 mcg/kg [81]. - The median overall survival (OS) for ICI resistant patients receiving the triple combination was reported at 21 months, significantly higher than the historical median OS of 3-4 months [85]. - The objective response rate (ORR) in ICI naïve patients with the triple combination was reported as 88%, compared to less than 25% with FDA-approved ICIs in HPV-positive cancers [85]. Vaccine Development - The company presented data on its investigational universal flu vaccine, PDS0202, demonstrating broad neutralization across multiple influenza strains [24]. - The company is developing a universal influenza vaccine using the Infectimune® platform, aiming for long-lasting protection against multiple strains of the virus [73]. - A second preclinical publication in February 2023 demonstrated complete protection in animal studies with PDS0202, a novel recombinant investigational protein-based universal flu vaccine [75]. - PDS0202, a universal influenza vaccine candidate, demonstrated significant hemagglutinin inhibition titer levels ranging from 28x to 62x compared to COBRA antigens alone in preclinical studies [112]. Clinical Trial Results - In June 2023, the company presented data showing a progression-free survival (PFS) rate of 55.2% and an overall survival (OS) rate of 87.2% at 9 months follow-up in the ICI naïve cohort [91]. - Estimated 12-month overall survival rate for PDS0101 in combination with Keytruda® is 87.1%, compared to published results of 36-50% for approved ICIs used alone [92]. - Median progression-free survival (PFS) for PDS0101 is 10.4 months, significantly higher than the published median PFS of 2-3 months for approved ICIs [92]. - Disease control rate for PDS0101 is 70.6%, with a confirmed and unconfirmed objective response rate of 41.2% [92]. - 24-month overall survival rate for PDS0101 is 74%, compared to less than 30% for approved ICIs [97]. - 12-month overall survival rate for PDS0101 is 80%, while published results for approved ICIs range from 30-50% [97]. - 60% of patients treated with PDS0101 experienced tumor shrinkage, with a confirmed overall response rate of 27% [97]. - PDS0101 treatment resulted in 81.3% clearance of circulating tumor DNA (ctDNA) after 3 weeks, compared to 30.3% with standard-of-care [103]. Product Pipeline and Development - The current development pipeline includes PDS01ADC + Versamune® HPV for recurrent or metastatic HPV16-positive HNSCC, with Phase 1/2 trials anticipated in 2024 for colorectal cancer [117]. - The company plans to seek marketing authorization from the FDA for its product candidates through the Biologics License Application pathway [130]. - The company plans to progress its preclinical product candidate PDS0103 to an IND submission in 2024 and advance to first-in-human trials [130]. - The company has engaged with the FDA for initial feedback on the clinical trial design for the PDS0103 program, which will influence its regulatory submission strategy [130]. - The company has identified over 75 tumor antigens and is exploring the expansion of its Versamune® based pipeline to develop additional product candidates [67]. Financial and Regulatory Considerations - The company has not generated any product revenue to date and has incurred net losses each year since its inception [116]. - The company relies on third-party contract manufacturing organizations for the production of its product candidates necessary for preclinical research and clinical studies [126]. - The company does not intend to incur costs for building its own manufacturing facilities in the near term, relying instead on external contract manufacturers [128]. - The company has developed a scalable manufacturing process for its product candidates, ensuring reproducibility and efficiency [126]. - The FDA's approval process includes multiple stages, such as preclinical tests, IND submission, and clinical trials, which can take many years [158]. - The FDA may require a Risk Evaluation and Mitigation Strategy (REMS) to ensure the safe use of a biological product, which can affect market potential [178]. - The approval of a BLA may be limited to specific diseases and dosages, impacting the commercial value of the product [181]. - The FDA may impose restrictions on product distribution and prescribing based on post-marketing studies or surveillance programs [182]. Collaborations and Agreements - The company executed an exclusive global license agreement with Merck KGaA for the tumor targeting IL12 fused antibody drug conjugate, M9241, which is now part of its pipeline [21]. - The company made a one-time cash payment of $5.0 million and issued 378,787 shares valued at $5.0 million to Merck KGaA for exclusive rights to develop and commercialize NHS-IL12 fusion protein (PDS01ADC) [136]. - Milestone payments to Merck KGaA could total up to $11 million upon achieving specific milestones, including the dosing of the fifth patient in a Phase 3 trial [137]. - The company has a Patent License Agreement with NIH for a therapeutic cancer vaccine using Versamune® technology, with various royalty obligations including a minimum annual royalty of $5,000 and 2% on net sales [142]. - The NCI Patent License Agreement allows the company to develop TARP peptide-based therapies, with royalties and benchmark payments tied to clinical milestones [143]. - A cost reimbursement agreement with the University of Kentucky Research Foundation was renewed for an anticipated cost of $628,171, terminating on June 30, 2024 [146]. - The company is collaborating with MSD International GmbH in a Phase 2 clinical trial to evaluate the combination of PDS0101 and Merck's pembrolizumab for treating head and neck cancer [148]. Competitive Landscape - The biotechnology and pharmaceutical industries are characterized by intense competition, with major companies such as Johnson & Johnson, Sanofi-Aventis, and Pfizer involved in similar research and development [153]. - The company anticipates facing increasing competition as new immunotherapies enter the market, which may affect its market position [155]. Compliance and Regulatory Challenges - Regulatory approval processes for biological products require substantial time and financial resources, with potential delays due to FDA holds [157]. - The FDA requires a significant application fee of $3,242,026 for each BLA requiring clinical data for fiscal year 2023 [175]. - Annual program fees for approved BLAs are set at $393,933 per eligible product for fiscal year 2023 [175]. - Fast track, breakthrough therapy, and priority review designations are available for products addressing unmet medical needs, facilitating expedited review [184][186][187]. - The FDA can withdraw approval if post-approval studies are not conducted or if clinical benefits are not confirmed [191]. - The Drug Supply Chain Security Act imposes obligations on manufacturers for product tracing and compliance within the drug supply chain [195]. - Non-compliance with FDA requirements can lead to severe enforcement actions, including product recalls and fines [198].