Versamune® Platform

 

Priming the immune system to unleash powerful and targeted attacks against cancer cells

The Versamune® nanotechnology platform is based on novel and structurally-specific synthetic and positively-charged lipids, that we believe are capable of:

1. Facilitating in-vivo the processing and presentation of tumor antigens into the MHC Class I and MHC Class II pathways, leading to effective priming of both CD8+ (killer) T-cells, which can attack and kill tumor cells, and CD4+ (helper) T-cells. Effective priming and activation of both types of T-cells results in robust anti-tumor responses.

2. Local stimulation of the immunological pathway known as the Type I Interferon  Pathway within lymph nodes.  This critical pathway is utilized by the body to elicit, activate and expand the CD8+ T-cell population.

3. Altering tumor micro-environment and biology by dramatically increasing the ratio of killer T-cells to the population of immune-suppressive cells, therefore making tumors much more susceptible to killing by CD8+ T-cells.

Versamune® Unique, multiple mechanism of action promotes strong in-vivo killer T-cell induction

Activation of these mechanisms by Versamune®:

• Results in a powerful killer T-cell response in-vivo that targets cancer cells, is effective in overcoming cancer tumor immune suppressing mechanisms, and thus effectively induces tumor cell death.

• Leads to the induction of a strong memory T-cell response. Induction of memory T-cells enables the body to generate tumor-attacking T-cells for an extended period of time after treatment.

Versamune® lipids are then hydrolyzed (broken-down) and excreted from the body, which we believe makes them well tolerated and safe.

Versamune® works when administered in the presence of a disease or cancer-specific protein “antigen” to efficiently enable the immune system to internalize, process, and present the antigen to the T-cells.  This process primes T-cells to effectively recognize each Versamune®-presented antigen.

Activating and directing the immune system to unleash a powerful and targeted attack against cancer cells with cationic lipids – a novel approach to effective immunotherapy

Versamune® Platform Activates Three Critical Mechanisms of Cancer Immunotherapy

The flow chart below summarizes how Versamune®-based products work to generate a potent anti-tumor effect after they are administered by subcutaneous injection.

 

PDS0101 Phase 1/2a Clinical Study

 

Successful Induction of In-Vivo Strong CD8+ T-cell Responses in Humans

Versamune®’s ability to prime in-vivo high levels of the right phenotype of active Granzyme-B inducing, antigen-specific CD8+ killer T-cell responses has been demonstrated in a Phase 1/2a human clinical trial.

PDS completed a Phase 1/2a trial of PDS0101, which was conducted at three sites in the United States. The study was an Open-label Escalating Dose Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of PDS0101 in subjects with Cervical Intraepithelial Neoplasia (CIN) and high-risk Human Papillomavirus (HPV) infections. The study included 3 cohorts of 3 to 6 subjects each, based on a modified “3 + 3” dose-escalation study design.

This study enrolled Cohort 1 and progressed through Cohort 3, with each subsequent cohort receiving a higher dose of PDS0101. Successive cohorts all receives a constant dose of the HPV-16 E6 and E7 antigens. Subjects were given three subcutaneous injections of PDS0101, three weeks apart, and blood was drawn 14-19 days after each injection, as well as 90 days after the last injection.

HPV-specific CD8+ T-cells were quantified using both the Interferon- ELISPOT assay (quantities all HPV-specific T-cells) granzyme-b ELISPOT assay (specifically quantifies active HPV-specific CD8+ T-cells). Dosing and dose escalation were based on safety evaluation for determination of potential dose-limiting toxicity (DLT).

A total of 12 subjects were enrolled. Strong induction of active HPV-specific killer T-cells (CD8+) was observed, with quantifiable amounts of the CD8+ T-cells retrieved from patient blood as late as 14-19 days after treatment.

 

Product Pipeline

 

Developing Broad Product Pipeline with Leaders in Immuno-Oncology

Versamune® is being developed both as a monotherapy and in combination with proven cancer treatments.  Powerful enhancement of anti-tumor efficacy and survival when Versamune®-based products are combined with checkpoint inhibitors has been demonstrated in multiple preclinical tumor models studies.

PDS0101

We believe PDS0101, our lead product candidate, can fundamentally improve patient outcomes and transform the management of HPV-related pre-cancers and cancers. PDS0101 utilizes a combination of Versamune® and various peptides from oncogenic strains of the HPV virus.

PDS0101 in Cervical Intraepithelial Neoplasia (CIN)

HPV-induced cancers, including cervical cancer, are one of the few cancer types with a well-defined pre-cancerous stage. Pre-cancerous lesions are defined as low-grade squamous intraepithelial lesions, including early stage cervical intraepithelial neoplasia (“CIN1”), and high grade squamous intraepithelial lesions, including late-stage cervical intraepithelial neoplasia (“CIN2/3”). There are currently no FDA-approved therapeutic drugs available to treat HPV-induced pre-cancers.

PDS0101 + Keytruda® in HPV-positive recurrent or metastatic head and neck cancer

PDS has a collaboration agreement with Merck and Co. to combine PDS0101 with Merck’s checkpoint inhibitor Keytruda® in a Phase 2 human clinical trial to treat HPV-positive recurrent or metastatic head and neck cancer.

PDS0102 (TARP-expressing cancers) for the treatment of prostate and breast cancers

Based on Phase 2 clinical trials run by the NCI using TARP antigens, PDS and the NCI are collaborating to develop a Versamune® platform-based immunotherapy for prostate cancer.

PDS0103 (MUC-1 expressing cancers) for the treatment of colorectal, breast, ovarian and lung cancers

PDS0103 is based on novel agonist antigens of the mucin-1 (MUC-1) oncogenic C-terminal region developed by the laboratory of Dr. Jeff Schlom, head of Tumor Biology at the National Cancer Institute. MUC1 is highly expressed in multiple tumor types and has been shown to be associated with drug resistance and poor prognosis for a range of human tumors. These agonist peptides, compared with native peptides, more efficiently enhance production of IFN-γ by peptide-activated human T-cells, and also more efficiently lyse human tumor cell targets in an MHC-restricted manner. MUC-1 antigens have been licensed from the NCI for use with Versamune® in ovarian, breast, colorectal and lung cancers.

PDS0104 (TRP2 expressing cancers) for the treatment of melanoma

PDS has completed preclinical work in advanced melanoma tumor models, where we observed the ability of PDS0104 to overcome immune suppression and inhibit growth of B16 melanoma tumors.