The AdAPT Platform

Designed to Target Cancer & Activate the Immune System

EpicentRx’s AdAPT Platform is based on an adenovirus (better known as the “common cold”) that has been uniquely altered to preferentially infect well in cancer and activate an immune response through a controlled cancer-targeted infection. This “viral vector” was developed after decades of research under Dr. Tony R. Reid, Professor of Oncology at University of California at San Diego (UCSD) and Chief Executive Officer at EpicentRx. The company has several anticancer therapies under development using this proprietary viral vector (studied under the name TAV-255), with each product exploring different ways to eliminate cancer defense mechanisms and activate the immune system – either alone or in combination with checkpoint inhibitors.

Preclinical studies have well characterized TAV-255’s ability to preferentially infect and kill cancer cells, coupled with proprietary modifications (altered from a normal common cold virus) to prevent replication in healthy cells. Through extensive experience in immuno-oncology research including his first-hand experience as a practicing medical oncologist of 25 years, Dr. Reid is an expert in the “oncolytic” (cancer infecting and killing) virus immunology arena. 

EpicentRx currently has two clinical stage programs under the AdAPT Platform:

  • AdAPT-001  An oncolytic adenovirus that is enhanced to express a TGF-β (beta) trap fusion protein.
  • Personalized Viruses (PSV)  Cancer patients have specific mutations present that are known to be cancer specific (also known as neoantigens). These patient-specific mutations are identified and used in development of a “personalized” virus that once infecting the patient’s tumors the mutation signal is amplified to alert the immune system.  

The figure below shows how an “oncolytic” virus works. Infecting and replicating well in cancer cells, leading to cell death (known as “lysis”), but designed to not damage healthy cells.

 

 

AdAPT-001 not your average Immunotherapy

Immunotherapy treatments generally given systemically and are designed to activate the immune system, but have no way of specifically pointing at the cancer and telling the immune system “this is your target”. An oncolytic virus like AdAPT-001 is designed to preferentially infect and spread an infection within malignant tumors – making cancer a target for the immune system.

However, the body is good at clearing out an infection and then shutting off the immune response through mechanisms like the TGF-beta protein, which turns off highly effective t-cells. Cancer utilizes the TGF-beta protein to protect against being eliminated by t-cells. So how can the immune system (t-cells particularly) remain active once the AdAPT-001 targeted infection has been cleared? The Answer: AdAPT-001 programs infected cancer cells to produce a TGF-beta “trap” molecule that is designed to neutralize TGF-beta within the infected tumor. Eliminating the t-cell silencing TGF-beta protein allows for the immune system to remain activated against cancer and this is what makes AdAPT-001 unlike any other immunotherapy.

AdAPT-001 doesn’t just create a cancer targeted infection, it produces a proprietary TGF-beta “trap” protein to eliminate this tumor defense mechanism and allow for sustained immune response against cancer – alone or in combination with immune checkpoint inhibitors.

AdAPT Platform Optimized Manufacturability

Manufacturing pharmaceutical grade gene therapy vectors at the scale needed for large phase trials and commercialization has historically been challenging, and EpicentRx has designed its manufacturing process to meet this challenge. Our viral vectors are engineered to maximally preserve the virus’s replication potential and reach high titers in our producer cell line where homologous recombination with the vector is not a concern. Upstream growth in suspension cultures with animal derived component free media and downstream purification processes are each designed for scalability from early phase trials to commercial production.

A current barrier for biological products to enter clinical testing is prohibitively long lead times with outsourced manufacturing. To overcome this bottleneck, EpicentRx created its own licensed GMP facility in California where new products can enter production rapidly with personnel who are dedicated and highly familiar with our products and processes.