TEL AVIV, Israel—Seeking to breach significant barriers and make up for lost time, Compugen Ltd., a leading predictive drug discovery company, has presented landmark findings from studies of CGEN-15029, the lead internal program in the company’s immuno-oncology therapeutics pipeline and treatment for metastatic melanoma—opening the door to what it deems a “new era of oncological inquiry and medicine.”
Compugen unveiled its promising results Feb. 29 before the New York Academy of Sciences’ Cancer Immunotherapy Conference, in a presenation entitled “Emerging Approaches to Cancer Immunotherapy.”
Compugen reported that initial validation studies show that expression of CGEN-15029 in T cells inhibits their activation by melanoma cells, consistent with an immune-suppressive role of the target in the tumor microenvironment. The target possesses signature immune-checkpoint receptor characteristics, including expression in relevant subsets of T cells and natural killer cells, with particularly high expression in lymphocytes that populate the tumor microenvironment (known as tumor infiltrating lymphocytes).
A binding partner for CGEN-15029 has also been identified, enabling a clear path toward selection of inhibitory antibodies and their therapeutic development. CGEN-15029 is Compugen’s highest-priority mAb program and was selected to be advanced toward clinical testing.
The key to Compugen’s status as a leading therapeutic discovery company is in utilizing its broadly applicable predictive discovery infrastructure to identify novel drug targets and develop first-in-class biologics. The primary focus of the company’s current pipeline is on immune checkpoint target candidates discovered by the company, potentially providing the basis for the next generation of therapeutics for cancer immunotherapy.
“For over a decade, we have been developing predictive platforms for a variety of biological processes and phenomena that are continuously being improved and diversified to address the need for novel targets in areas of interest to the industry,” says John Hunter, site head and vice president of antibody research and development at San Francisco-based Compugen USA.
CGEN-15029 is one of the multiple novel immune checkpoint target candidates discovered through Compugen’s unique in-silico predictive discovery capabilities.
Targeting the body’s immune system to detect and destroy cancer cells, cancer immunotherapy is now being applied to hematological malignancies, non-small cell lung cancer and other solid tumors, Hunter notes. Areas of promising investigation such as checkpoint blockade inhibitors, specific T cell engagers (bi-specific antibodies), tumor cell-directed vaccines and adoptive T cell therapies are significantly altering treatment and outcomes.
However, issues with the identification of optimal target antigens, understanding of mechanisms of action and strategies to combat treatment resistance remain barriers to an in-depth understanding of this cancer therapy, he said.
“The results for CGEN-15029 are important from two aspects,” Hunter tells DDNews. “One, they demonstrate our continued advancement of our lead internal program in the company’s immuno-oncology therapeutics pipeline. More specifically, our identification of a binding partner during CGEN-15029’s target validation efforts has provided a much clearer path toward discovery and development of therapeutic antibodies against the target.”
And two, “the results are also a further validation of the power of our predictive discovery infrastructure,” he says.
“Based on its predicted immune response modulation and the target expression pattern, we believe that the drug blocking CGEN-15029 activity will be relevant for a number of different tumor types, and we are currently exploring which cancer types we will focus on in the clinic,” Hunter explains.
Dr. Anat Cohen-Dayag, Compugen president and CEO, stated recently: “We are now at the stage of selecting the therapeutic clinical candidate which we plan to advance to IND, and we are finalizing work plans for such advancement on various fronts, including manufacturing, preclinical and regulatory.”
Immuno-oncology represents a paradigm shift in the treatment of cancer, according to Cohen-Dayag, who also noted: “In 2010, we directed our predictive discovery spotlight on the ﬁeld of immune checkpoints as the company’s ﬁrst focused application of its discovery infrastructure, with a goal of addressing the unmet need for novel, effective cancer immunotherapies. Within a few months of predictive discovery work, we signiﬁcantly enriched the more than 20-year-old ﬁeld of immune checkpoints with the discovery of 11 novel immune checkpoint drug target candidates.”
“Today, our unique predictive discovery capabilities have resulted in one of the broadest and most promising novel target pipelines for immuno-oncology in the industry,” Cohen-Dayag added. “Our pipeline includes multiple opportunities for ﬁrst-in-class therapeutics addressing areas of unmet medical need in oncology.
“Although to date, the blockade of immune checkpoints has proven effective for only a minority of patients in a limited—but growing—number of cancer types, it has provided impressive clinical benefits, enabling long-term survival—even for end-stage patients—and is transforming cancer therapeutics,” she went on to note.
Immune checkpoints are inhibitory receptors and their ligands, which are crucial for the maintenance of self-tolerance (that is, the prevention of autoimmunity) and for the protection of tissues from damage when the immune system is responding to pathogenic infection or other injuries.
These immune checkpoints, which are “hijacked” by tumors to block the ability of the immune system to destroy the tumor (immune resistance), have emerged as promising targets for cancer immunotherapy, and have shifted the treatment paradigms for several major cancer types, Compugen states. Therapeutic blockade of immune checkpoints boosts antitumor immunity, enabling the patient’s immune system to recognize and attack the tumor cells and to mount durable antitumor responses and tumor destruction.