Compugen Ltd., a Tel Aviv, Israel, based leading drug discovery company focused on monoclonal antibodies and therapeutic proteins to address important unmet needs in the fields of oncology and immunology, announced today positive initial experimental results for the first two of five in silico, or by computer, predicted targets for antibody drug conjugate or ADC cancer therapy disclosed in late 2013.

The two candidates demonstrate low expression levels in normal critical tissues, such as heart and liver, and higher expression in multiple cancer types, such as colorectal and prostate cancers for which there is high unmet medical need.

Research & Development
The available results suggest that the two target candidates may serve for the development of ADC therapy in oncology. Initial validation of the remaining three candidates, and further testing of these two, is ongoing. It is expected that a therapeutic antibody discovery program against a selected ADC target will commence later this year.

Antibody-drug conjugates (ADC) based cancer therapy destroys cancer cells by delivering high-potency cytotoxic agents (the “payload”) directly to the cancer cells. The principle underlying ADC therapy is to impact only the cancer cells by linking the cytotoxic agent payload to an antibody or antibody fragment that specifically binds to a protein that is present on cancer cells and expressed at lower levels in healthy cells. When administered to the patient, the antibody with the payload specifically targets this protein, and is internalized into the cells, where the toxic payload is released and activated. Thus, unlike traditional chemotherapies, ADCs are designed to specifically destroy only cells displaying the cancer target protein. ADCs against a number of targets, both in solid and hematologic tumors, are in clinical development by biopharma companies, and two ADC products have obtained FDA regulatory approval in the past two years.

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Photo: Anat Cohen-Dayag, PhD, Compugen’s President and CEO.  Photo courtesy: Compugen, Ltd, Tel Aviv, Israel.

“As previously disclosed, most of our R&D and commercialization efforts are now being directed towards immuno-oncology related activities supporting our immune checkpoint based candidates for immunotherapy. As these very promising candidates based on our first discovery program move ahead, we look forward to further broadening the scope and diversity of our Pipeline Program with therapeutic antibodies against ADC targets resulting from our second discovery program. We therefore are very pleased to report these initial positive experimental results in this additional area of high industry interest, supporting the therapeutic potential of these first two target candidates and further demonstrating the unique capabilities of our broadly applicable predictive discovery infrastructure,” explained Anat Cohen-Dayag, PhD, Compugen’s President and CEO.

LEADS and MED Program
Compugen’s Monoclonal Antibody (mAb) Targets Discovery Platform predicts the existence of proteins that can serve as targets for antibody therapeutics. The company’s program relies heavily on it’s propitiary LEADS and MED capabilities, two computational – in silicon – biology infrastructure platforms that serve as core components for the development discovery platforms.

The LEADS platform provides a comprehensive view of the human transcriptome, proteome and peptidome, and serves as a rich infrastructure for the discovery of novel genes, transcripts and proteins. It includes extensive gene information and annotation, such as splice variants, antisense genes, SNPs, novel genes, RNA editing, etc.  At the protein level, LEADS provides full protein annotation, including homologies, domain information, sub-cellular localization, peptide prediction, and novelty status.

The MED Platform is an integrated database composed of the results from more than 70,000 public and proprietary microarray experiments, normalized and organized into approximately 1,400 therapeutically relevant conditions (i.e., normal tissues, malignant tissues, tissues from drug treated patients). Utilizing a sophisticated query interface, the proprietary MED platform allows the simultaneous examination of the expression of genes and pathways across all 1,400 conditions and tissues as well as all 70,000 microarray experiments.

To date Compugen predicted most ADC targets in clinical development by industry and discovered five potential new cancer targets for ADC therapy.

Immune checkpoint candidates
In December 2014 Compugen announced the initiation of a multi-year research collaboration with Johns Hopkins University, School of Medicine under the direction of Prof. Drew Pardollm MD,PhD, Abeloff Professor of Oncology, Medicine, Pathology, and Molecular Biology and Genetics at Johns Hopkins University of Medicine, and Charles Drake,MD, PhD, members of Compugen’s Scientific Advisory Board and pioneers in the field of immuno-oncology.

This collaboration will focus on further evaluation of selected novel B7/CD28-like immune checkpoint candidates discovered by Compugen for the potential treatment of cancer. This evaluation will include the candidates’ differentiation profile with respect to known checkpoints and their potential to serve either for monotherapy or in combination with other cancer treatments.

Work on Compugen’s novel target discovery program is performed by Compugen’s wholly-owned U.S. subsidiary located in South San Francisco, USA.

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