Compugen Announces Discovery of Two Novel Immune Checkpoint Targets for Cancer Immunotherapy
Compugen Ltd. (NASDAQ: CGEN), announced today the discovery and initial validation of two new drug target candidates for monoclonal antibody (mAb) cancer therapy. These new candidates have been shown to be expressed in multiple types of tumors and were shown to have an immunomodulatory activity in affecting both innate and adaptive immune responses, thus providing the potential for an efficient and targeted approach in cancer treatment. By offering a different mode of action from Compugen's other immune checkpoint candidates, these molecules further broaden the scope of the Company's Pipeline Program for monoclonal antibody treatment of cancer.
In recent in vitro studies, both of these immune checkpoint molecules have shown distinct activity inhibiting two key subtypes of immune cells, Natural Killer (NK) cells and T cells. These key immune cell subtypes act to recognize and kill tumor cells and have critical roles in the response of the immune system to tumor development. Antibodies directed against and blocking each of these immune checkpoints could remove their inhibitory effect on T cells and NK cells, thus enhancing the anti-tumor activity of these pivotal immune cell subsets. Therefore, agents targeting these checkpoint molecules hold great promise for efficient cancer immunotherapy and long-lived tumor destruction.
Recent protein expression studies for these two Compugen-discovered molecules indicate enhanced expression in a wide variety of cancers with high unmet medical need. These include lung, ovarian, breast, colorectal, gastric and liver cancer. Hence, in addition to their potential utility in cancer immunotherapy, which aims to stimulate the patient's own immune system to eliminate cancer cells, these two molecules also have therapeutic potential as drug targets for direct cancer mAb therapy, whereby monoclonal antibodies directed against these targets would directly destroy the cancer cells.
Dr. Anat Cohen-Dayag, President and CEO of Compugen, stated, “It is increasingly evident that the blockade of immune checkpoints is among the most promising approaches to activate therapeutic anti-tumor immunity. Therefore, we are very pleased with the addition of the two immune checkpoint targets being disclosed today, each of which acts on both arms of the immune system."
Dr. Cohen-Dayag continued, "These two molecules broaden Compugen's oncology pipeline, thus potentially providing differentiated and effective solutions for multiple forms of cancer. In this respect, we recently reported that CGEN-15001, an Fc fusion protein based on the Compugen-discovered CGEN-15001T immune checkpoint target, promotes inducible regulatory T cells (iTregs) in addition to its inhibitory effect on T cells. Therefore, an antibody directed against and blocking CGEN-15001T has the potential to eliminate the inhibitory effect of this molecule on T cells and, in parallel, to inhibit iTregs' pro-tumorigenic effects. Given the current scientific understanding that multiple modes of action will be required for effective cancer treatments, our pipeline now includes a number of distinct oncology product candidates, including the two being disclosed today, further attesting to the predictive strength of our in silico approach to drug discovery."
About Immune Cells, Checkpoint Proteins and Cancer
Natural Killer cells, T cells, and iTregs, are key immune cells in the innate and adaptive immune responses, and all are modulated by immune checkpoint proteins. The innate immune response provides the body with a general first line of defense against pathogens, while the adaptive immune response endows the immune system with long-lasting and protective memory in preparation for future assaults by the same antigen.
NK cells are the front line troops of the innate immune system, constantly on patrol for pathogens or tumor cells. NK cells aim to recognize and kill tumor cells, and as such have become a subject of intensive investigation in the field of tumor immunology. NK cell-mediated killing of tumor cells depends on the balance between stimulatory and inhibitory pathways. Thus, antibody blockade of NK inhibitory pathways is a promising strategy to enhance NK cell activity and is an emerging treatment modality for cancer immunotherapy.
T cells are major players in the potent adaptive immune response to detect and destroy tumor cells. However, negative costimulatory immune checkpoint proteins expressed by the cancer cells often are responsible for the suppression of the anti-tumor activity of these T cells. As such, T-cell based immunotherapy, which aims to initiate or augment T cell responses against tumor cells, is an attractive new approach in cancer treatment.
iTregs are immunosuppressive cells accumulating in the tumor microenvironment and in the circulation of patients with cancer, and are responsible for the suppression of the anti-tumor capacity of the immune system. Tumor progression thus benefits from the immunosuppressive effects mediated by iTregs. Inhibition of these cells is also considered one of the most promising approaches for cancer treatment, as it would enhance anti-tumor immunity and increase the efficacy of cancer immunotherapy.
Tumors develop specific immune resistance mechanisms. An important immune resistance mechanism involves immune-inhibitory pathways, termed immune checkpoints, which are expressed on immune cells, mainly activated by T cells and iTregs, and also NK cells. Clinical studies employing mAb blockade of immune checkpoints, such as PD-1 and CTLA4, have shown unprecedented durable responses and a possible cure of metastatic disease. Antibodies targeting immune checkpoints have been thus termed “the next frontier" in the treatment of cancer.
Compugen is a leading therapeutic product discovery company focused on therapeutic proteins and monoclonal antibodies to address important unmet needs in the fields of immunology and oncology. Unlike traditional high throughput trial and error experimental based discovery, Compugen utilizes a broad and continuously growing integrated infrastructure of proprietary scientific understandings and predictive platforms, algorithms, machine learning systems and other computational biology capabilities for the in silico (by computer) prediction and selection of product candidates, which are then advanced in its Pipeline Program to the pre-IND stage. The Company's business model primarily involves collaborations covering the further development and commercialization of product candidates from its Pipeline Program and various forms of research and discovery agreements, in both cases providing Compugen with potential milestone payments and royalties on product sales or other forms of revenue sharing. In 2012, Compugen established operations in California for the development of oncology and immunology monoclonal antibody therapeutic candidates against Compugen-discovered drug targets. In 2002, Compugen established an affiliate, Evogene Ltd., (www.evogene.com) (TASE: EVGN.TA), to utilize certain of the Company's in silico predictive discovery capabilities in agricultural biotechnology. For additional information, please visit Compugen's corporate website at www.cgen.com.
This press release may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as “may,” “expects,” “projects,” “anticipates,” “believes” and “intends,” and describe opinions about future events. Forward-looking statements in this press release include, but are not limited to, that agents targeting the two Compugen-discovered checkpoint molecules hold great promise for efficient and long-lived tumor destruction, that these two molecules also have therapeutic potential as drug targets for direct cancer mAb therapy, and that an antibody directed against and blocking CGEN-15001T has the potential to eliminate the inhibitory effect of this molecule on T cells and, in parallel, to inhibit iTregs pro-tumorigenic effects. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Some of these risks are: changes in relationships with collaborators, including, without limitation, corporate partners or licensees; the impact of competitive products and technological changes; risks relating to the development of new products in general; risks relating to the research, development, regulatory approval, manufacturing or marketing of new therapeutic or diagnostic products; the ability to implement technological improvements; and risks related to obtaining necessary resources, including, without limitation, capital. These and other factors are discussed in the "Risk Factors" section of Compugen's Annual Report on Form 20-F for the year ended December 31, 2011 as filed with the Securities and Exchange Commission. In addition, any forward-looking statements represent Compugen's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law.
Tsipi Haitovsky, Global Media Liaison