TARGETS CANCER, IMMUNE ACTIVATION
The AdAPT Immunotherapy Platform is developed on a genetically modified version of the human adenovirus (common cold virus) that has been designed to preferentially infect and kill cancer cells – belonging to a class of virus-based cancer therapies known as “oncolytic viruses.”
AdAPT Platform immunotherapies turn “cold” tumors “hot” by creating a controlled infection within a treated tumor, alerting an innate immune response, promoting inflammation within the tumor, and programming the adaptive immune system to seek out an destroy metastatic disease throughout the body and prevent recurrence.
Oncolytic immunotherapy is an emerging class of cancer-targeting therapeutics based on genetically altered viruses that have been modified to preferentially infect, replicate in, and kill cancer cells (while sparing healthy cells).
Activation of the immune system against cancer has had some success with the development of immune checkpoint inhibitors (i.e. PD-L1, PD-1, CTLA-4), however, their effectiveness in indicated cancers remains low. In addition, prolonged treatment with checkpoint inhibitors can develop into debilitating autoimmune disorders where the immune system attacks healthy cells.
When combined with an immune checkpoint inhibitor, oncolytic viruses represent a way to enhance other immunotherapies by directing a potent immune response to the cancer and, when effective, doing it with a shorter treatment duration.
TARGETS CANCER, DISABLES DEFENSES
Immunotherapy treatments are 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.
Cancer survives by suppressing the immune system and tumor expression of transforming growth factor beta (TGFβ) is a key factor
However, the body is good at clearing out an infection and then shutting off the immune response through mechanisms like the TGF-beta (TGFβ) protein, which turns off highly effective T-cells. So how can the immune system (especially T-cells) remain active once the AdAPT-001 targeted infection has been cleared?
AdAPT-001 doesn’t just create a cancer-targeted infection, it produces a proprietary TGFβ “trap” protein to eliminate this tumor defense mechanism and allow for sustained immune response against cancer – alone or in combination with immune checkpoint inhibitors.
Personalized Virus Program
(investigational clinical stage)
Patients with cancer have mutations that are cancer specific, known as neoantigens. These neoantigens are identified using genetic sequencing of a patient’s cancer. Once identified, the neoantigens are incorporated into a custom (personalized) AdAPT virus. The personalized virus is administered to the patient where the virus is designed to specifically target and replicate in cancer cells while amplifying the neoantigen signal to alert and activate the immune system to target the cancer.
Neoantigens are ideal targets for the immune system because they are expressed in tumors but not in normal cells. These personalized viruses have been engineered produce thousands of copies of themselves, spreading an immune activating infection within the tumor, and expressing the patient specific neoantigens that they are carrying. The personalized virus is administered to the patient and is designed to preferentially infect tumors while amplifying the patient’s unique neoantigen signature. The virus replicates well in cancer and spreads the infection throughout the tumor, generating an immune response. The responding immune system is then given a sample of the patient’s neoantigens to train the immune system to recognize cancer throughout the body.
First Ever Patient-Specific Cancer Targeting Virus
EpicentRx produced the first ever clinically administered personalized cancer targeting virus “armed” with neoantigens or peptide fragments from the patient’s tumors.
AdAPT™ Platform Manufacturability
Manufacturing pharmaceutical grade gene therapy vectors at the scale needed for large phase trials and commercialization has historically been challenging. 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. 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.
To overcome this bottleneck, EpicentRx has 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.
AdAPT™ Platform Administration
Our AdAPT Platform treatments utilize intratumoral (direct injection) administration, resulting in high concentrations of the therapeutic agent delivered to tumors.
However, at EpicentRx we’re committed to developing treatments that are available to all cancer patients and not only those with injectable tumors. For patients with inaccessible tumors, we’re working closely with UC San Diego research center to develop methods for IV (systemic) delivery of AdAPT viruses using nanoparticle encapsulation technology.
Nanoparticle Encapsulation Technology
Through jointly developed IP we have encapsulated AdAPT viruses and have tested them in ongoing animal studies. Encapsulation methods have shown improved tumor infection when administered IV and better efficacy in some cancers when given by direct tumor injection. Future clinical studies will include encapsulated virus treatments with systemic delivery in certain cancer patient populations.