BIOECLIPSE THERAPEUTICS™ IS WORKING TO IMPROVE CANCER STATISTICS FOR PATIENTS
OUR FUNDAMENTAL PREMISE IS THAT CANCER HAS MULTIPLE CAUSES AND CHALLENGES THAT REQUIRES A MULTI-MECHANISTIC APPROACH
The BioEclipse Approach
The pioneering work underway at BioEclipse Therapeutics approaches cancer immunotherapy from not just one, but several directions. We believe that to defeat cancer requires a drug with multiple mechanisms of action (MOA) that work synergistically and systemically to target and kill cancer cells all over the body, and at the same time, create a durable immune response that prepares the patient’s body to fight relapse and recurrence.
With our lead drug candidate, CRX100, we have used an intellectual property portfolio, developed by the company’s founders and exclusively licensed from Stanford University, to create a first-in-class immunotherapy that pairs the power of an oncolytic virus with the tumor-locating ability of cytokine-induced killer (CIK) cells. What is truly novel, is how this multi-modal therapy overcomes limitations that, until now, have hobbled the efficacy of cellular and oncolytic viral therapies.
How CIK Cells and Oncolytic Viruses Work Together to Kill Tumors
Patient-derived killer cells are treated ex-vivo with cytokines to create activated CIK cells, which are innate immune cells programmed to seek out, find and then kill cancer cells. The CIK cells are then infected with vvDD (vaccinia virus, double deletion). The virus hides inside the CIK cells until reaching the cancer cell, where the virus harnesses the cancer cell’s RAS oncogene pathway to explode and kill the cancer cell.
The antitumor effect of the combination of cytokine-induced killer (CIK) cells and attenuated vaccinia virus show that our CIK cells carry the oncolytic virus to the tumor bed in about 48-72 hours, after which a rapid burst of viral replication kills the tumor cells. When the virus is carried by CIK cells, it can reach tumors away from the vasculature. This produces more uniform distribution of viral infection within the tumor, which contributes to sustained viral gene expression and increased tumor destruction in-vivo.
Studies have demonstrated that there is a synergy between the cytotoxic effect of CIK cells and the oncolytic effect of the virus against tumor cells. The key attributes of this synergy are the protection of the virus by the CIK cells from immune system destruction, and the ability of the CIK cells to activate the immune response in the tumor microenvironment, thereby increasing the potency CRX100 significantly compared to using cells or virus alone.
Understanding The Problem
Cancer is one of the leading causes of death around the world, and the number of incidences, especially those linked to social and economic developments in growing populations, are increasing at an alarming rate. Progress in understanding cancer biology and the immune system has fueled major advances in cancer treatments, but the current standard of care in oncology falls short for many patients with hard-to-treat cancers. BioEclipse Therapeutics has focused our research and development on creating a combined product that meets the needs of patients with recurring and resistant cancers. Our lead drug candidate, CRX100, was developed to overcome these inherent challenges:
PROBLEM: Drug Resistance
Resistant tumor cells grow in the presence of most cancer drugs. For instance, more than 70% of ovarian cancer patients have progressive tumors that are resistant to standard-of-care therapies.
BIOECLIPSE SOLUTION: A combination therapy with multiple mechanisms of action
CIK cells naturally locate, infiltrate and destroy tumor cells. This allows CIK cells to carry and deliver our oncolytic virus directly into the tumor bed where the virus and the immune cells work separately, but systematically, to attack cancer cells.
PROBLEM: High Toxicity to Healthy Cells
Most tumor-killing agents also attack normal cells and cause toxicity and other side effects.
BIOECLIPSE SOLUTION: Our therapy is designed to be selective in killing tumor cells.
CIK cells are the natural immune surveillance and killing mechanism for abnormal cells, including infected and cancerous cells. CIK cells bind to and kill cancer cells while releasing the oncolytic virus directly in the tumor. Also, our oncolytic vaccinia virus is highly attenuated to allow replication in tumor cells, but not in healthy cells.
PROBLEM: Tumors Can Create Signals That Block Drugs
Tumors use a variety of tricks to evade the immune system. Tumor cells can hide by changing their cell surface to become invisible to immunotherapies.
BIOECLIPSE SOLUTION: Our therapy attacks tumors on multiple fronts
CIK cells can carry the oncolytic virus across the vasculature and breach the tumor’s protective environment, where it then attaches to tumor cells. The virus is released, infects the tumor and works to kills cells and make the tumor more susceptible to our immunotherapy. Viral infection of the tumor causes an increase in expression of stress ligands on the cell surface which signals the immune system to attack of the tumor. Viral destruction of tumor cells also makes tumor antigens highly visible to the immune system.
PROBLEM: Disease Recurrence
Drug resistance and tumor immune evasion can leave behind metastatic or residual disease after treatment with standard therapies, leading to recurrence.
BIOECLIPSE SOLUTION: Durable immune response against multiple tumor antigens
CIK cells produce chemicals that attract the other cells in the adaptive immune system, including antigen presenting cells, cytotoxic T-cell and T-helper cells. Together these cells generate a response against tumor antigens from lysed tumor cells. This is a memory immune response that allows the adaptive immune system to continue identifying and destroying cancerous cells after the initial treatment.
PROBLEM: The Immune System’s Anti-Viral Response
Injection of oncolytic viruses directly into the tumor is an inefficient method to kill tumors throughout the body. Oncolytic viruses delivered through the blood leaves the virus open to attack by the neutralizing anti-viral responses of a patient’s immune system, which kills the virus before it can reach the tumors. This prevents the virus from reaching the tumor and hinders repeat treatment.
BIOECLIPSE SOLUTION: Our platform delivers the oncolytic virus inside the CIK cells
CIK cells camouflage the virus in the blood and ferry the virus to tumor cells allowing the virus to reach the tumors unassaulted by the immune system. The CIK cells can deliver the virus directly to the sites of metastatic disease. Cancerous cells act as viral production factories which allows the virus to replicate and destroy many more cancer cells. Our therapy uses immune cells expanded and activated outside of the body which means they do not continue to replicate after reinfusion and thus have reduced side effects.
PROBLEM: Cell Therapies Don’t Work On Solid Tumors
CAR-T and other engineered T-cell therapies face unique challenges finding, entering and surviving in solid tumors. So, while these therapies have shown encouraging results in hematologic cancers, efficacy against solid tumors has proved elusive.
BIOECLIPSE SOLUTION: CIK cells bring the virus in close proximity to the tumor cells which allows tumor lysis by the virus
CIK cells are specifically and innately designed to travel to tumor cells to eradicate the abnormal cells without requiring the identification of specific tumor antigens. CIK cells can overcome the immunosuppressive tumor microenvironment and with the multi-faceted MOAs can induce an anti-tumor response from within the tumor bed. Once inside the tumor cell, the virus begins replication and increases stress ligands on the tumor cell surface to elevate the tumor visibility to the immune system.