Our Approach

Pendrea’s robust underlying technology offers multiple opportunities for the development of products for the treatment of cancer.  The breadth of the potential pipeline is striking both in the products it can produce, but also in the different mechanisms used to create these products.  Pendrea has two distinct product platforms, both of which are based on completely novel approaches to the treatment of cancer.  

 

1. Ceraxa restores the efficacy of approved therapeutics in Relapsed and Refractory patients

 

Ceramide is a natural anticancer agent in the body that is depleted during chemotherapy.  The only known means of delivering ceramide exogenously is via Ceraxa, which is a stable nanoliposome embedding C-6 ceramide (a cancer fighting form of ceramide) in its outer membrane for delivery to the interior of cancer cells.  By replacing the depleted levels of ceramide exogenously with Ceraxa, Pendrea is able to restore the activity of standard of care therapeutics.  

 

Pendrea is targeting Ceraxa for restoration of efficacy for relapsed and refractory (R&R) patients in several cancers.  First generation Ceraxa can be co-administered with standard of care therapeutics.  Second generation forms of Ceraxa, in which standard of care chemotherapeutics are encapsulated in the hollow core of the nanoparticle, are in development.  The inclusion of an approved therapeutic within Ceraxa creates a single product that mitigates the potential toxic effects of the chemotherapeutic while also restoring its efficacy.  

 

This 2nd generation “Ceraxa Plus” platform offers the potential for development of any number of different products resulting in a continual expansion of Pendrea’s pipeline and its partnering opportunities.  The opportunity to restore activity to standard of care chemotherapeutics that have lost their effectiveness is sorely needed and is a critical unmet need that only Ceraxa can address.

 

1. New Approaches to Immuno-Oncology

 

Pendrea also has an exciting immuno-oncology program that uses three different technical approaches, all of which are proprietary and are differentiated from competitive approaches.

 

Ceraxa is a potent immunotherapeutic agent  --  Ceraxa provides a unique and proprietary mechanism for reversing tumor induced immunosuppression and restoring the ability of the immune system to kill cancer cells.  Ceraxa binds a specific phosphatase inducing a broad de-phosphorylation cascade that in addition to inducing apoptosis, also (1) down regulates pro-cancerous signaling in cancer cells, and (2) switches tumor associated macrophages in the tumor microenvironment from the pro-cancerous M2 phenotype to the anti-cancer M1 phenotype.  In response, cancer specific cytotoxic T cells are increased, while pro-cancerous mitogens are highly down regulated.  This novel and broad acting immuno-therapeutic approach can work as a monotherapy or in synergy with other immunotherapeutic approaches, e.g. with checkpoint inhibitors, Car T and adoptive cell therapy with tissue specific antigens.

 

Photo Immuno Nano Therapy (PINT)  --  PINT is a completely novel system using harmless near infrared light (nIR) and indocyanine green, an imaging agent in use in humans for the past 40 years, encapsulated in NanoJackets (NJs), which are non-toxic calcium-phosphosilicate nanoparticles that deliver active agents to the interior of the cell.  NanoJackets, which can be “actively” targeted to specific cell types, enter the targeted cell by pinocytosis and release their active agents via pH change once inside the cell.  

 

PINT has a dual mechanism of action that involves direct killing of cancer cells and activation of the immune system.  PINT causes direct killing of cancer cells by high efficiency Photo Dynamic Therapy (PDT).  When indocyanine green is delivered to the interior of the cell photodynamic efficiency is exponentially increased resulting in generation of Reactive Oxygenated Species (ROS) and cancer cell death.  PINT also generates a sphingosine kinase that reduces inflammation in the tumor microenvironment resulting in T-cell attack on tumors.  This dual mechanism of action has produced dramatic preclinical results in a completely non-toxic system.  

 

RNA Therapeutics (RNA NJs)  --  NanoJackets with active targeting moieties on their surface deliver RNA to the interior of targeted cells resulting in highly efficient RNA expression.  The RNA NJ system, which is made of biologically compatible materials, avoids the toxicities associated with LNPs (Lipid Nano Particles) and therefore provides a unique and important alternative to LNP based RNA therapeutics.  The RNA encapsulated in the NJs, which is protected from degradation in the blood stream, can code for therapeutic and prophylactic vaccines as well as therapeutic proteins.

 

1. Competitive Differentiation

 

Delivery of Ceramide  --  The chemotherapeutic utility of ceramide has been limited by its extremely low solubility.  While solubility is inversely related to the length of the fatty acid chain, systemic delivery of even short chain ceramides is limited by precipitation in aqueous solutions, poor cell permeability and metabolism (degradation) in vivo.  Ceraxa overcomes these limitations and enables systemic administration of ceramide.  Pendrea’s proprietary technology, which embeds c-6 ceramide in the outer membrane of a nanoparticle, makes the therapeutic use of ceramide possible.  

 

Restoration of efficacy to chemotherapeutics in Relapsed & Refractory Patients  --  No other company or product has ever been able to restore efficacy to standard of care chemotherapeutics that have lost their effectiveness either due to the development of resistance or because the patient was refractory to the therapeutic approach in the first place.  Ceraxa has shown in numerous animal studies that it is able to restore efficacy to a wide range of standard of care therapeutics.  The ability to do so without adding any toxicity to the already approved therapeutics offers Ceraxa a wide range of opportunity for development of therapeutic combination products.

 

Immuno-Oncology  --  Pendrea’s approach to immuno-oncology is both proprietary and totally unique.  Running through three separate technologies  --  Ceraxa, PINT and RNA Therapeutics  --  Pendrea offers entirely new ways to approach immune therapy for cancer.

• Ceraxa  --  provides a unique direct killing mechanism as well as resuscitation of the cellular (T-cell) immune system resulting in a highly effective dual mechanism for tumor cell death.

• PINT  --  the delivery of indocyanine green to the interior of cancer cells by NanoJackets results in a dual mechanism of direct killing and induction of the cellular immune system (T-cells) that is a totally unique and non-toxic approach to cancer therapy.

• RNA Therapeutics  --  Pendrea’s NanoJacket system is a proprietary, highly efficient means for delivery of RNA to activate the immune system and to deliver mRNA therapeutics to specific tumors.  It offers a non-toxic alternative to existing RNA delivery systems.